Immunotherapy Options Research Articles

Comparative effectiveness of combination first-line therapies for metastatic renal cell carcinoma (mRCC).

e16549 Background: Numerous immunotherapy (IO) and vascular endothelial growth factor receptor inhibitors (VEGFI) options are approved for first-line (1L) treatment of mRCC. We performed a systematic review and meta-analysis to compare the oncologic outcomes and adverse events of these therapies. Methods: We searched databases for randomized controlled trials (RCT) evaluating agents that are currently FDA-approved or on the NCCN compendium for 1L mRCC, with sunitinib (S) as a comparator. Primary outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 and 4 (G3/G4) adverse events (AEs). We attempted network meta-analysis (NMA) to estimate relative effects of the comparative treatments. Survival outcomes were summarized using hazard ratios (HR). In the case that the HR was not reported but a Kaplan-Meier curve was available, the curve was digitized using Engauge Digitizer software. A frequentist fixed-effects NMA model was applied to each outcome. Results: 798 articles were identified, of which 47 were eligible for full text screening, and 8 were included for evidence synthesis. Eight RCTs recruiting a total of 5,565 pts with advanced or metastatic treatment-naïve RCC were included. The summary of all included studies is reported in Table 1. Ordered from the most to least effective, treatments with greatest mOS benefit include Nivolumab plus Cabozantinib (NC), Pembrolizumab plus Axitinib (PA), and Nivolumab plus Ipilimumab (NI); treatments with greatest mPFS benefit include Cabozantinib (C), NC, and Avelumab plus Axitinib (AA); treatments with the highest ORR include C, NC, and AA. Ordered from least to most toxic, treatments with G3/G4 AEs less frequent than sunitinib include Pazopanib (P), NI, and AA. Conclusions: OS generally favored IO-IO or IO-VEGFI combinations, while PFS and ORR favored single agent C or IO-VEGFI. The lowest risks of G3/G4 AE were seen with P or IO-IO. IO-VEGFI combinations had similar risks for G3/G4 AE. Longer real-world follow-up is needed. We recognize the limitations of cross-trial comparisons, but sought a summative view of the current data.[Table: see text]

Efficacy and safety of vactosertib and pembrolizumab combination in patients with previously treated microsatellite stable metastatic colorectal cancer.

3573 Background: Microsatellite stable metastatic colorectal cancer (MSS mCRC) represents a high unmet need since there are currently no approved immunotherapy options. Since the inhibition of the transforming growth factor-β (TGF-β) pathway is known to contribute to the enhancement of immunotherapy efficacy, here, we report the results of vactosertib, a potent and selective TGF-β receptor I kinase inhibitor, combined with pembrolizumab in patients with MSS mCRC. Methods: In this phase 2, open label trial, patients have received vactosertib (300 mg BID, 5 days on / 2 days off) and pembrolizumab (200 mg, every 3 weeks) until confirmed progressive disease (PD), unacceptable toxicity or consent withdrawal. Patients with histologically confirmed mCRC who had disease progression after treatment with all available therapies including fluoropyrimidine and oxaliplatin or irinotecan were enrolled. Eligible patients were ≥19 years old, had ECOG status ≤1, and had no prior exposure to immunotherapy. The objectives were to evaluate the safety and efficacy (objective response rate (ORR) per RECIST v1.1). Results: Thirty-three patients with MSS mCRC were enrolled. Median age was 60 (range 33-72), 55% were male, median number of previous lines of chemotherapy was 3 (range 1-7), and 82% were consensus molecular subtype (CMS) 4. The ORR was 15.2% including 5 partial responses (PRs), 7 stable diseases, and 17 PDs as best overall responses; 12 patients remain on treatment. Among 5 patients with PR, 3 patients had confirmed PR and median duration of response was not reached yet. As of 04 Jan 2021, the most common treatment related adverse events (AEs) were increased amylase (21.2%), pruritus (21.2%), rash (21.2%), and increased lipase (18.2%). There were 3 treatment-related SAEs reported; drug induced pneumonitis (3%), nausea (3%), and vomiting (3%). Conclusions: The combination treatment with vactosertib and pembrolizumab showed favorable safety profile with promising efficacy in patients with MSS mCRC. Updated data including pharmacodynamic markers will be presented at the meeting. Clinical trial information: NCT03724851.

Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC.

TPS9135 Background: Effective immunotherapy options are lacking for patients with advanced non-small cell lung cancer (NSCLC) who progress on a programmed cell death-(ligand)1 [PD-(L)1] inhibitor and for those that are epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement positive after progression on tyrosine kinase inhibitor (TKI) therapy. One potential approach to improve immune checkpoint efficacy in these patient populations is to promote cytolytic T cell infiltration into tumors. This can be accomplished via in situ vaccination with functional antigen presenting cells (APCs) which can take advantage of the full repertoire of tumor antigens and convert the tumor into a lymph node-like environment promoting both local and systemic T cell activation. The chemokine CCL21 promotes co-localization of naive T cells and antigen-experienced dendritic cells (DCs) to facilitate T cell activation. Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in systemic antitumor immunity. However, increased PD-L1 expression was observed in some patient tumors, suggesting that tumor-mediated impairment of T cell function may be forestalling a more robust CCL21-DC mediated antitumor response. Similarly, improved PD-(L)1 inhibitor efficacy may be possible with enhanced T cell infiltration and augmented APC function following IT CCL21-DC. Therefore, we are conducting a phase I trial, combining IT CCL21-DC with pembrolizumab in patients with advanced NSCLC that are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy. Methods: Phase I, dose-escalating, multi-cohort trial followed by dose expansion. Maximum of 24 patients (9-12 escalation + 12 expansion) with stage IV NSCLC will be evaluated who have tumors accessible for IT injection and are either (1) EGFR/ALK wild-type after progression on a PD-(L)1 inhibitor or (2) EGFR/ALK mutant after progression on TKI therapy. Three IT injections of autologous CCL21-DC (days 0, 21, 42) will be concurrently administered with pembrolizumab, followed by q3wk pembrolizumab up to 1 year. Primary objective of dose escalation is safety and determination of maximum tolerated dose (MTD) of IT CCL21-DC (5x106, 1x107, or 3x107) when combined with pembrolizumab. Primary objective of dose expansion is objective response rate at MTD. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment. Clinical trial information: NCT03546361.

Facility contextual effects influence the use of adjuvant immunotherapy in stage III melanoma.

e18758 Background: There are now numerous effective adjuvant immunotherapy options for surgically resected stage III melanoma including novel checkpoint inhibitors and targeted therapies. Current guidelines recommend that the decision to treat stage III melanoma with adjuvant immunotherapy should be individualized and based upon disease burden, patient goals and anticipated therapy tolerance. We sought to assess the contribution of patient, tumor and facility factors on the implementation of immunotherapy in patients with surgically resected stage III melanoma. Methods: Using the National Cancer Database (NCDB), patients from 2012-2017 that underwent excision and were found to have a positive sentinel node were identified. A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and facility variables on the probability of immunotherapy. Reference Effect Measures (REM) were used to estimate the variation in immunotherapy use due to unmeasured facility factors (contextual effects) after adjusting for measured patient, tumor, and facility variables. Results: From 2012 to 2017, the percent of patients with stage III melanoma treated with adjuvant immunotherapy increased from 23.7% to 38.5% (p < 0.05). Overall, younger patients and patients with private insurance were more likely to receive immunotherapy. Tumor factors associated with increased use of adjuvant immunotherapy included increasing depth, mitotic rate ³1, ulceration, lymphovascular invasion (LVI), and undergoing a completion lymph node dissection (CLND). Additionally, treatment at a facility with a surgical volume <190 cases/year was associated with increased immunotherapy use. However, the width of the 90% REM range for unmeasured facility effects exceeded that of the measured facility, tumor, time, and patient demographics suggesting that contextual effects had a higher contribution to the variation in immunotherapy use. Conclusions: Our analysis suggests that uninsured patients and patients with government insurance (Medicaid and Medicare) are not receiving immunotherapy at the same frequency as privately insured patients with the same tumor characteristics treated at the same facility. Lastly, compared to known patient, tumor and facility factors, institutional contextual effects were the major drivers of the implementation of immunotherapy.[Table: see text]

Nuclear overexpression levels of MAGE‐A3 predict poor prognosis in patients with prostate cancer

Melanoma antigen gene A3 (MAGE-A3) is one of the most immunogenic cancer testis antigens and is common in various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE-A3 in 153 prostate tissue samples including prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HPIN). Increased both nuclear and cytoplasmic expression of MAGE-A3 was significantly found in PCa tissues compared with both HPIN and BPH tissues (nuclear expression at p=0.011, and cytoplasmic expression at p=0.034; for both comparisons p<0.0001, respectively). A significant correlation was observed between higher nuclear and cytoplasmic expressions of MAGE-A3 with Gleason score (p<0.0001 and 0.006, respectively). Increased expression of MAGE-A3 was associated with shorter biochemical recurrence-free survival (BCR-FS) and disease-free survival (DFS) of patients (p=0.042 and =0.0001, respectively). In multivariate analysis, nuclear expression of MAGE-A3 and Gleason score (≤7 vs >7) was independent predictors of the DFS (both; p=0.019). Nuclear expression of MAGE-A3 was also significantly related to BCR-FS (p=0.015). MAGE-A3 can be considered as a predictor for poor prognosis and an option for vaccine immunotherapy in patients with PCa.

T-Cell Receptor Therapy in the Treatment of Ovarian Cancer: A Mini Review.

Ovarian cancer, in particularly high-grade serous ovarian cancer (HGSOC) and ovarian carcinosarcoma (OCS), are highly aggressive and deadly female cancers with limited treatment options. These tumors are generally unresponsive to immune check-point inhibitor (ICI) therapy and are referred to as immunologically “cold” tumors. Cell-based therapy, in particular, adoptive T-cell therapy, is an alternative immunotherapy option that has shown great potential, especially chimeric antigen receptor T cell (CAR-T) therapy in the treatment of hematologic malignancies. However, the efficacy of CAR-T therapy in solid tumors has been modest. This review explores the potential of another cell-based therapy, T-cell receptor therapy (TCR-T) as an alternate treatment option for immunological “cold” OC and OCS tumors.

Novel Therapies in the Treatment of Hodgkin Lymphoma.

Patients with Hodgkin lymphoma (HL) can achieve excellent response and survival rates following frontline combination chemo- and radiation therapy. However, about 10-15% of patients will experience disease relapse which is associated with poor outcomes. Recent breakthroughs in understanding the mechanisms of oncogenicity and interactions within the tumor microenvironment have resulted in development of novel drugs for treatment of patients with HL. Utilizing this information, treatment of newly diagnosed and relapsed HL has become a rapidly evolving field with multiple clinical trials evaluating novel treatment approaches incorporating targeted immunotherapy. In the frontline setting, the use of novel drugs may allow for de-escalation of therapy to avoid long-term complications associated with bleomycin and consolidation radiation therapy. Patients with early-stage, non-bulky disease are candidates for omitting radiation therapy using treatment combinations that include upfront use of brentuximab vedotin or nivolumab. In patients with advanced disease, the addition of brentuximab vedotin to a chemotherapy backbone is currently the standard of care in our practice, particularly in patients with a contraindication for receiving bleomycin. Future investigations in patients with advanced-stage HL will focus on establishing a new standard of care by comparing brentuximab vedotin and nivolumab in combination with chemotherapy (BV-AVD vs. N-AVD) and decreasing the risk of relapse by exploring consolidation therapy in patients with high-risk disease. In patients who have relapsed or are refractory to first-line therapy, salvage treatment has incorporated brentuximab vedotin or PD-1 checkpoint inhibitors to improve response rates of cytotoxic chemotherapy thereby improving the probability of a successful stem cell transplant. Post-transplant consolidation with brentuximab is currently standard of care in patients with high-risk disease. Patients who relapse following autologous stem cell transplant now have an expanded armamentarium of chemo- and immunotherapy options. However, the challenge is to determine the sequence of therapy after prior brentuximab or checkpoint inhibitor exposure.

Immune-Inhibitory Gene Expression is Positively Correlated with Overall Immune Activity and Predicts Increased Survival Probability of Cervical and Head and Neck Cancer Patients.

Background: Limited immunotherapy options are approved for the treatment of cervical cancer and only 10–25% of patients respond effectively to checkpoint inhibition monotherapy. To aid the development of novel therapeutic immune targets, we aimed to explore survival-associated immune biomarkers and co-expressed immune networks in cervical cancer. Methods: Using The Cancer Genome Atlas (TCGA) Cervical Squamous Cell Carcinoma (CESC) data (n = 304), we performed weighted gene co-expression network analysis (WGCNA), and determined which co-expressed immune-related genes and networks are associated with survival probability in CESC patients under conventional therapy. A “Pan-Immune Score” and “Immune Suppression Score” was generated based on expression of survival-associated co-expressed immune networks and immune suppressive genes, which were subsequently tested for association with survival probablity using the TCGA Head Neck Squamous Cell Carcinoma (HNSCC) data (n = 528), representing a second SCC cancer type. Results: In CESC, WGCNA identified a co-expression module enriched in immune response related genes, including 462 genes where high expression was associated with increased survival probability, and enriched for genes associated with T cell receptor, cytokine and chemokine signaling. However, a high level of expression of 43 of the genes in this module was associated with decreased survival probability but were not enriched in particular pathways. Separately, we identified 20 genes associated with immune suppression including inhibitory immune checkpoint and regulatory T cell-related genes, where high expression was associated with increased survival probability. Expression of these 20 immune suppressive genes (represented as “Immune Suppression Score”) was highly correlated with expression of overall survival-associated immune genes (represented as “Pan-Immune Score”). However, high expression of seven immune suppression genes, including TWEAK-R, CD73, IL1 family and TGFb family genes, was significantly associated with decreased survival probability. Both scores also significantly associated with survival probability in HNSCC, and correlated with the previously established “Immunophenoscore.” Conclusion: CESC and HNSCC tumors expressing genes predictive of T cell infiltrates (hot tumors) have a better prognosis, despite simultaneous expression of many immune inhibitory genes, than tumors lacking expression of genes associated with T cell infiltrates (cold tumors) whether or not these tumor express immune inhibitory genes.

The Role of Immune Checkpoint Molecules for Relapse After Allogeneic Hematopoietic Cell Transplantation.

Immune checkpoint molecules represent physiological brakes of the immune system that are essential for the maintenance of immune homeostasis and prevention of autoimmunity. By inhibiting these negative regulators of the immune response, immune checkpoint blockade can increase anti-tumor immunity, but has been primarily successful in solid cancer therapy and Hodgkin lymphoma so far. Allogeneic hematopoietic cell transplantation (allo-HCT) is a well-established cellular immunotherapy option with the potential to cure hematological cancers, but relapse remains a major obstacle. Relapse after allo-HCT is mainly thought to be attributable to loss of the graft-versus-leukemia (GVL) effect and hence escape of tumor cells from the allogeneic immune response. One potential mechanism of immune escape from the GVL effect is the inhibition of allogeneic T cells via engagement of inhibitory receptors on their surface including PD-1, CTLA-4, TIM3, and others. This review provides an overview of current evidence for a role of immune checkpoint molecules for relapse and its treatment after allo-HCT, as well as discussion of the immune mediated side effect graft-vs.-host disease. We discuss the expression of different immune checkpoint molecules on leukemia cells and T cells in patients undergoing allo-HCT. Furthermore, we review mechanistic insights gained from preclinical studies and summarize clinical trials assessing immune checkpoint blockade for relapse after allo-HCT.

Hypoxia enhances the production and antitumor effect of exosomes derived from natural killer cells

BackgroundExosomes are a subgroup of extracellular vesicles that are naturally released by almost all types of cells. However, the factors that promote the capacity of natural killer (NK) cells to release exosomes are unclear. In this study, we investigated whether hypoxia can enhance the yield of NK cell-derived exosomes and improve the immunotherapeutic effects of these cells.MethodsExosomes from NK92 or NK92-hIL-15 cells were isolated from culture medium under normoxic (NK92-Exo and NK92-hIL-15-Exo) or hypoxic (hypoxic NK92-Exo and hypoxic NK92-hIL-15-Exo) conditions. NK92-Exo and hypoxic NK92-Exo were characterized by transmission electron microscopy (TEM), nanoparticle-tracking analysis (NTA), and western blot. Real-time cell assay, wound healing assay, flow cytometry, and western blot were then performed to assess cytotoxicity, cell proliferation, cell migration, apoptosis, and the expression levels of cytotoxicity-associated proteins.ResultsAfter 48 hours of hypoxic treatment, NK92-Exo exhibited significantly increased cytotoxicity, enhanced inhibition of cell proliferation, and elevated levels of molecules associated with NK cell cytotoxicity. The hypoxia-treated NK92-Exo and NK92-hIL-15-Exo showed increased expression of three functional proteins of NK cells—specifically FasL, perforin, and granzyme B—as compared with their NK92-Exo counterparts exposed to normoxia.ConclusionsAs an approach that supports overproduction of exosomes, hypoxic treatment of NK cells may serve as a promising therapeutic option for cancer immunotherapy.

Comparative efficacy and safety of immunotherapy in the first-line treatment of metastatic renal cell carcinoma: a systematic review and network meta-analysis.

With the advances in immune checkpoint inhibitor therapy, several novel treatment options for metastatic renal cell carcinoma (mRCC) patients have recently emerged. The present study explored the optimal first-line immunotherapy for mRCC through a Bayesian network meta-analysis of the latest research data. PubMed, MEDLINE, EMBASE, American Society of Clinical Oncology (ASCO) meeting abstracts, and the Cochrane Library were searched up to July 2020 to identify any randomized controlled trials related to immunotherapy in the first-line treatment of mRCC. The primary outcome was progressionfree survival, and the secondary outcomes were overall survival and grade 3-4 adverse events. The network meta-analysis included 4,049 patients from 5 randomized controlled trials. Avelumab plus axitinib and pembrolizumab plus axitinib were the best treatment options in terms of progression-free survival. For overall survival, pembrolizumab plus axitinib had a 77.89% probability of being the preferred treatment. For adverse events, there was an 89.21% probability that pembrolizumab plus axitinib was the regimen with the worst side effects. Through a meta-analysis of the latest available first-line immunotherapy progression-free survival and overall survival data for mRCC, this study found that pembrolizumab plus axitinib might be the best immunotherapy option for first-line treatment. However, attention should be paid to the potential adverse events of this regimen.

Meeting Proceedings of the 2nd Annual Immuno-Oncology Society of India Conference (I-OSICON-2020), Mumbai, India.

Meeting Proceedings of the 2nd Annual Immuno-Oncology Society of India Conference (I-OSICON-2020), Mumbai, India.

Unleashing the power of immunotherapy and targeted therapy combinations: Advancing cancer care or discovering unknown toxicities?

The purpose of this review was to summarize the triumphs and pitfalls of tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) combinations.Data sources: A literature review of PubMed was conducted and studies were included if they were classified as a clinical trial and assessed TKI and ICI combinations for solid tumor malignancies. Dates of literature search included January 1, 1988 through September 22, 2019.Data summary: In the past decade, TKI and ICI monotherapy strategies have changed the management of many advanced solid tumors through their unique mechanisms of action. Preclinical data suggests that TKIs may be able to sensitize tumors to ICI therapy via direct and indirect pathways; however, optimal mechanisms to support various TKI and ICI combinations have yet to be determined. The FDA recently approved TKI and ICI combinations for renal cell carcinoma, endometrial carcinoma, and melanoma. Several other tumor types currently have TKI and immunotherapy combinations under investigation with mixed results. Dual therapy with TKIs and immunotherapy have the potential to be synergistic and improve patient outcomes; however, careful consideration will need to be taken in regard to what TKI and immunotherapy are combined. Future research will be needed to determine appropriate sequencing of TKIs and ICIs after progression on combination therapy. Continued research is necessary to determine optimal dual TKI and immunotherapy options.

A Novel Design of Multi-epitope Vaccine Against Helicobacter pylori by Immunoinformatics Approach.

Helicobacter pylori (H. pylori) is a gram-negative spiral bacterium that caused infections in half of the world’s population and had been identified as type I carcinogen by the World Health Organization. Compared with antibiotic treatment which could result in drug resistance, the vaccine therapy is becoming a promising immunotherapy option against H. pylori. Further, the multi-epitope vaccine could provoke a wider immune protection to control H. pylori infection. In this study, the in-silico immunogenicity calculations on 381 protein sequences of H. pylori were performed, and the immunogenicity of selected proteins with top-ranked score were tested. The B cell epitopes and T cell epitopes from three well performed proteins UreB, PLA1, and Omp6 were assembled into six constructs of multi-epitope vaccines with random orders. In order to select the optimal constructs, the stability of the vaccine structure and the exposure of B cell epitopes on the vaccine surface were evaluated based on structure prediction and solvent accessible surface area analysis. Finally Construct S1 was selected and molecular docking showed that it had the potential of binding TLR2, TLR4, and TLR9 to stimulate strong immune response. In particular, this study provides good suggestions for epitope assembly in the construction of multi-epitope vaccines and it may be helpful to control H. pylori infection in the future.Supplementary InformationThe online version of this article (10.1007/s10989-020-10148-x) contains supplementary material, which is available to authorized users.

CanImmunother: a manually curated database for identification of cancer immunotherapies associating with biomarkers, targets, and clinical effects

ABSTRACT As immunotherapy is evolving into an essential armamentarium against cancers, numerous translational studies associated with relevant biomarkers, targets, and clinical effects have been reported in recent years. However, a large amount of associated experimental data remains unexplored due to the difficulty in accessibility and utilization. Here, we established a comprehensive high-quality database for cancer immunotherapy called CanImmunother (http://www.biomedical-web.com/cancerit/) through manual curation on 4515 publications. CanImmunother contains 3267 experimentally validated associations between 218 cancer sub-types across 34 body parts and 484 immunotherapies with 642 biomarkers, 108 targets, and 121 control therapies. Each association was manually curated by professional curators, incorporated with valuable annotation and cross references, and assigned with an association score for prioritization. To help clinicians and researchers in identifying and discovering better cancer immunotherapy and their respective biomarkers and targets, CanImmunother offers user-friendly web applications including search, browse, excel table, association prioritization, and network visualization. CanImmunother presents a landscape of experimental cancer immunotherapy association data, serving as a useful resource to improve our insight and to facilitate further discovery of advanced immunotherapy options for cancer patients.

Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients.

Most patients with diffuse large B-cell lymphoma (DLBCL) are diagnosed at age 60 years or older. Challenges to effective therapy among older individuals include unfavorable biologic features of DLBCL, geriatric vulnerabilities, suboptimal treatment selection, and toxicities of cytotoxic chemotherapy. Wider application of geriatric assessments may help identify fit older patients who benefit from standard immunochemotherapy without unnecessary dose reductions. Conversely, attenuated regimens may provide a better balance of risk and benefit for selected unfit or frail patients. Supportive care with the use of corticosteroid-based prephase, prophylactic growth factors, and early institution of supportive and palliative care can help maximize treatment tolerance. Several novel or emerging therapies have demonstrated favorable toxicity profiles, thus facilitating effective treatment for elderly patients. In the relapsed or refractory setting, patients who are not candidates for stem cell transplantation can benefit from newly approved options including polatuzumab vedotin-based combinations or tafasitamab plus lenalidomide, which may have higher efficacy and/or lower toxicity than historical chemotherapy regimens. Chimeric antigen receptor T-cell therapy has been successfully applied to older patients outside of clinical trials. In the first-line setting, emerging immunotherapy options (bispecific antibodies) and targeted therapies (anti-CD20 antibodies combined with lenalidomide and/or B-cell receptor inhibitors) may provide chemotherapy-free approaches for DLBCL. Enrolling older patients in clinical trials will be paramount to fully examine potential efficacy and toxicity of these strategies. In this review, we discuss recent advances in fitness stratification and therapy that have expanded curative options for older patients, as well as future opportunities to improve outcomes in this population. IMPLICATIONS FOR PRACTICE: Management of diffuse large B-cell lymphoma in older patients poses challenges due to aggressive disease biology and geriatric vulnerability. Although R-CHOP remains standard first-line treatment, geriatric assessment may help evaluate patients' fitness for immunochemotherapy. Corticosteroid prephase, prophylactic growth factors, and early palliative care can improve tolerance of treatment. Novel salvage options (polatuzumab vedotin-based combinations, tafasitamab plus lenalidomide) or chimeric antigen receptor T-cell therapy should be considered in the relapsed or refractory setting for patients ineligible for stem cell transplantation. Emerging immunotherapies (bispecific antibodies) and targeted therapies provide potential first-line chemotherapy-free approaches, which need to be rigorously assessed in clinical trials that involve geriatric patients.

Third Generation CD20 Targeted CAR T-Cell Therapy (MB-106) for Treatment of Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Third Generation CD20 Targeted CAR T-Cell Therapy (MB-106) for Treatment of Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

BackgroundPeptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide...

Black phosphorus quantum dots doped multifunctional hydrogel particles for cancer immunotherapy

Immunotherapy is a powerful approach for oncotherapy that relies on enhancing the ability of the immune system to recognize and attack tumors. Effectively provoking the immune effector cells to respond to cancer cells is still a challenge. Here, we present a novel kind of γδ T cell-stimulating hydrogel particle loaded with zoledronate for breast cancer immunotherapy. The hydrogel particles with interconnected nanopores were formed by negatively replicating silica colloidal crystal beads (SCCBs) through using N-isopropylacrylamide (NIPAM) pregel solution doped with black phosphorus quantum dots (BPQDs). Due to the photothermal-responsive property of the BPQDs doped pNIPAM hydrogel, the releasing of zoledronate from these particles could be accurately controlled by using deep penetrating near-infrared (NIR) light. Owing to the direct anti-tumor activity and the capacity of stimulating γδ T-cell to attack tumor cells, our BPQDs-doped pNIPAM hydrogel particles show great potential for γδ T cell activation and proliferation with high therapeutic efficacy for in vivo breast cancer treatment. Thus, the γδ T cell-stimulating hydrogel particles provide a novel clinical treatment option for cancer immunotherapy.

Immunotherapy in non-muscle-invasive bladder cancer: current status and future directions.

Patients harboring high-grade non-muscle-invasive bladder cancer (NMIBC) experience high rates of both recurrence and progression. Currently, few treatment options besides cystectomy exist for this at-risk population, especially those with BCG-unresponsive disease. The purpose of this review is to present the current status and describe future directions of immunotherapy in NMIBC. The PubMed and Google Scholar databases were searched for articles pertaining to immunotherapy in NMIBC. Relevant planned and ongoing clinical trials were identified using www.ClinicalTrials.gov . Published randomized control trials, reviews, other retrospective and prospective studies deemed relevant were used in this review paper. Novel immunotherapies used in the treatment of high-grade NMIBC and BCG-unresponsive disease allow patients more options and have the potential to reduce the need for radical cystectomy. Currently, several options target the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis as this mechanism of immunotherapy has been shown to be effective in several cancers, including bladder, melanoma, and lung cancers. In addition, other immunotherapy options for the treatment of NMIBC include viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines. The current landscape of immunotherapy in bladder cancer is rapidly evolving, with much literature pertaining to muscle-invasive and metastatic disease. However, the implementation of these treatment options in high-grade NMIBC may allow patients to avoid life-altering surgery. Reliable biomarkers for response are needed to further select patients who may benefit from such therapies.