Advances In Immunotherapy Research Articles

Recent advancements at ASCO 2024 in PD-L1 and PD-1 bispecific antibodies.

Recent advancements in cancer immunotherapy have spotlighted the PD-1/PD-L1 pathway, crucial for its role in immune checkpoint regulation. Traditional inhibitors, though successful, face challenges like resistance and adverse effects. Bispecific antibodies targeting PD-1 and PD-L1 present a ground-breaking solution by simultaneously engaging multiple immune regulatory molecules. Developments in PD-1/PD-L1 bispecific antibodies up to now have been summarized, and the latest findings from the 2024 ASCO conference are presented, revealing that bispecific antibodies exhibit robust efficacy in treating various types of cancers, marking a significant step forward in cancer treatment.

Immune microenvironment of cancer bone metastasis.

Bone is a common and frequent site of metastasis in cancer patients, leading to a significant reduction in quality of life and increased mortality. Bone marrow, the primary site of hematopoiesis, also serves as both a primary and secondary lymphoid organ. It harbors and supports a diverse array of immune cells, thereby creating a distinct immune microenvironment. These immune cells engage in a range of activities, including anti-tumor, pro-tumor, or a combination of both, which influence the development and progression of bone metastases. Rapid advances in cancer immunotherapy have underscored its potential to eradicate bone metastases. However, clinical outcomes have not yet met expectations. To improve the efficacy of immunotherapy, it is crucial to gain a comprehensive and in-depth understanding of the immune microenvironment within bone metastases. This review provides an overview of the current understanding of the role of different immune cells, their anti-tumor and pro-tumor activities, and their overall contribution to bone metastasis.

Contemporary Review of Adenocarcinoma of the Cervix.

Among cervical cancers, adenocarcinoma is less common than squamous cell carcinoma of the cervix; however, the incidence of these cancers is rising. The incidence has changed largely due to a shift in risk factors as well as the evolution of the diagnosis and classification of adenocarcinoma. Adenocarcinoma of the cervix is composed of a diverse group of neoplasms that can be classified by various factors. In this review article, preinvasive disease, updated classifications of adenocarcinoma, and treatment options for cervical adenocarcinoma are discussed with a focus on current and future therapies. Advances in antibody-drug conjugates (ADC) and immunotherapy have increased the treatment options available for usual-type adenocarcinoma but there is still a lack of variety of treatment options for the remaining 25% of non-usual-type adenocarcinomas.

Beyond the blood: expanding CAR T cell therapy to solid tumors.

Chimeric antigen receptor (CAR) T cell therapy stands as a transformative advancement in immunotherapy, triumphing against hematological malignancies and, increasingly, autoimmune disorders. After a decade of relatively modest results for solid tumors, recent clinical trials and patient reports have also started to yield promising outcomes in glioblastoma and other challenging solid tumor entities. This Perspective seeks to explore the reasons behind these latest achievements and discusses how they can be sustained and expanded through different strategies involving CAR engineering and synthetic biology. Furthermore, we critically analyze how these breakthroughs can be leveraged to maintain momentum and broaden the therapeutic impact of CAR T cells across a variety of solid tumor landscapes.

EXTH-40. IMMUNOPHENOTYPING OF RWTC-MBTA AUTOLOGOUS CANCER VACCINE IN PRECLINICAL GLIOBLASTOMA MODELS

Abstract Despite advances in immunotherapy, glioblastoma multiforme (GBM) remains challenging to treat due to its low inherent immunogenicity and a suppressive tumor microenvironment. Converting “cold” GBMs to “hot” tumors is crucial for effective immune activation and improved patient outcomes. We comprehensively characterized the rWTC-MBTA autologous cancer vaccine, consisting of Mannan-BAM-anchored irradiated whole tumor cells, Toll-like receptor ligands (LTA, Poly(I:C), R-848), and an anti-CD40 agonistic antibody, in preclinical GL261 and SB28 GBM models. A substantial number of vaccinated mice exhibited complete regression of GBM tumors in a T-cell-dependent manner, with no significant toxicity. Long-term tumor-specific immune memory was confirmed upon tumor rechallenge. In the vaccine-draining lymph nodes of the SB28 model, rWTC-MBTA vaccination triggered a major rise in cDC1 12 hours post-treatment, followed by an increase in cDC2, moDC, and pDC on Days 5 and 13. Enhanced cytotoxicity of CD4+ and CD8+ T cells in vaccinated mice was verified in co-culture with tumor cells. Comprehensive immunophenotyping in the GL261 and SB28 GBM microenvironments confirmed decreased regulatory T cells and increased CD4+ and CD8+ T cell infiltration in vaccinated mice. T-cell exhaustion analyses revealed an increase in the Tim3+CD8+ T cells. No significant differences were observed in the quantification of M-MDSC and PMN-MDSC between control and vaccinated mice, but PD-L1 expression significantly increased in M2 macrophages in vaccinated mice. Our findings demonstrate that rWTC-MBTA induces potent and long-term adaptive immune responses against GBM, warranting further investigation of combinations with other immunotherapies for enhanced efficacy.

TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial.

Relapsed/refractory peripheral T cell lymphomas (PTCLs) are aggressive tumors with a poor prognosis. Unlike B cell lymphomas, treatment of PTCL has not benefited from advances in immunotherapy. This is largely due to a lack of suitable target antigens that discriminate malignant from normal T cells, thus avoiding severe immunosuppression consequent to depletion of the entire T cell compartment. We recently described a targeting strategy based on the mutually exclusive expression of T cell antigen receptor beta-chain constant domain (TRBC) 1 and 2. Selective targeting of the T cell antigen receptor beta-chain expressed by the (clonal) malignancy spares normal T cells expressing the other chain. The LibraT1 study is an ongoing, multicenter, international, single-arm phase 1/2 study of TRBC1-directed autologous chimeric antigen receptor (CAR) T cells (AUTO4) in relapsed/refractory TRBC1-positive PTCL. Primary objectives were assessment of safety and tolerability of AUTO4 infusion. Key secondary endpoints included efficacy, CAR T cell expansion and persistence. Here we describe the findings from dose escalation in LibraT1 in the first ten patients, in a non-prespecified interim analysis. AUTO4 resulted in low frequency of severe immunotoxicity, with one of ten patients developing grade 3 cytokine release syndrome. Complete metabolic response was observed in four of ten evaluable patients, with remissions being durable beyond 1 year in two patients. While an absence of circulating CAR T cells was observed, CAR T cells were readily detected in lymph node biopsy samples from sites of original disease suggesting homing to tumor sites. These results support the continuing exploration of TRBC1 targeting in PTCL. ClinicalTrials.gov registration: NCT03590574 .

Advances in CAR NK Cell Therapy for Targeting and Eradicating Circulating Tumor Cells: Challenges and Solutions for Aging Patients Mini Review

Chimeric Antigen Receptor (CAR) Natural Killer (NK) cells represent a promising advancement in cancer immunotherapy, particularly for targeting circulating tumor cells (CTCs) and preventing metastasis. This review examines the latest developments in CAR NK cell therapy, including diverse NK cell sources, genetic engineering techniques, and dual mechanisms of action. Targeting CTCs with CAR NK cells shows significant potential in aggressive cancers like triple-negative breast cancer (TNBC) and pancreatic cancer. The impact of aging on NK cell function, especially regarding cytotoxicity, cytokine secretion, and persistence, poses challenges for elderly patients, but strategies such as interleukin-15 and metabolic interventions offer potential solutions. The review also addresses current limitations, such as poor persistence in immunosuppressive microenvironments and low solid tumor infiltration, while proposing combination therapies to enhance effectiveness. Although still in earlier clinical stages compared to CAR T cells, CAR NK cells’ safety profile and MHC-independent recognition mechanisms make them a versatile therapeutic option. Future directions include optimizing NK cell persistence, improving infiltration, and developing age-adapted therapies for elderly patients. _________________________________________________________________________________________ Keywords: CAR NK cells, CAR T cells, Circulating tumor cells (CTCs), Cell Therapy, Aging

High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype

BackgroundBreast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) and other immune regulation pathways in this neoplasia.MethodsIn this retrospective study, we evaluated the correlation of mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FOXO1 with clinicopathological factors and BC patient’s outcome by real-time quantitative polymerase chain reaction (qPCR).ResultsOur results showed that immunoregulatory gene expression depends on BC immunophenotype being CTLA-4 and PDCD1 (PD1) overexpressed on triple-negative/basal-like (TN/BL) and luminal B/HER2-positive phenotypes, respectively, and CD276 (B7-H3), JAK2 and FOXO1 associated with both luminal A and luminal B/HER2-negative tumors. In addition, we found that these genes can also be related to aggressive and non-aggressive clinicopathological characteristics in BC. Finally, survival analysis showed that CTLA-4 expression levels emerge as a significant independent factor of good prognosis in BC patients, especially in the HER2-enriched subtype.ConclusionConsidering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9

Optimizing cancer treatment has become a pivotal goal in modern oncology, with advancements in immunotherapy and genetic engineering offering promising avenues. CAR-T cell therapy, a revolutionary approach that harnesses the body’s own immune cells to target and destroy cancer cells, has shown remarkable success, particularly in treating acute lymphoblastic leukemia (ALL), and in treating other hematologic malignancies. While CAR-T cell therapy has shown promise, challenges such as high cost and manufacturing complexity remain. However, its efficacy in solid tumors remains limited. The integration of CRISPR/Cas9 technology, a powerful and precise genome-editing tool, also raises safety concerns regarding unintended edits and off-target effects, offers a synergistic potential to overcome these limitations. CRISPR/Cas9 can enhance CAR-T cell therapy by improving the specificity and persistence of CAR-T cells, reducing off-target effects, and engineering resistance to tumor-induced immunosuppression. This combination can also facilitate the knockout of immune checkpoint inhibitors, boosting the anti-tumor activity of CAR-T cells. Recent studies have demonstrated that CRISPR/Cas9-edited CAR-T cells can target previously untreatable cancer types, offering new hope for patients with refractory cancers. This synergistic approach not only enhances the efficacy of cancer treatment but also paves the way for personalized therapies tailored to individual genetic profiles. This review highlights the ongoing research efforts to refine this approach and explores its potential to revolutionize cancer treatment across a broader range of malignancies. As research progresses, the integration of CAR-T cell therapy and CRISPR/Cas9 holds the promise of transforming cancer treatment, making it more effective and accessible. This review explores the current advancements, challenges, and future prospects of this innovative therapeutic strategy.

Emerging strategies to overcome ovarian cancer: advances in immunotherapy

Ovarian cancer is the second most common malignant neoplasm of gynecological origin and the leading cause of death from cancer in the female reproductive system worldwide. This scenario is largely due to late diagnoses, often in advanced stages, and the development of chemoresistance by cancer cells. These challenges highlight the need for alternative treatments, with immunotherapy being a promising option. Cancer immunotherapy involves triggering an anti-tumor immune response and developing immunological memory to eliminate malignant cells, prevent recurrence, and inhibit metastasis. Some ongoing research investigate potentially immunological advancements in the field of cancer vaccines, immune checkpoint blockade, CAR-T cell, and other strategies.

Delayed and Concurrent Stereotactic Radiosurgery in Immunotherapy-Naïve Melanoma Brain Metastases

Melanoma remains a formidable challenge in oncology, causing the majority of skin cancer deaths in the United States, with brain metastases contributing substantially to this mortality. This paper reviews the current therapeutic strategies for melanoma brain metastases, with a focus on delayed and concurrent stereotactic radiosurgery (SRS). While surgery and traditional chemotherapy offer limited efficacy, recent advances in immunotherapy, particularly immune checkpoint inhibitors (ICIs), have played a major role in the advancement and improved efficacy of the treatment of cancers, including brain metastases. Recent studies indicate that monotherapy with ICIs may lead to a higher median overall survival compared to historical benchmarks, potentially allowing patients to delay radiosurgery. Other studies have found that combining SRS with ICIs demonstrates promise, with results indicating improved intracranial control. Ongoing clinical trials explore novel combinations of immunotherapies and radiotherapies, aiming to optimize treatment outcomes while minimizing adverse effects. As treatment options expand, future studies will be necessary to understand the interplay between therapies and their optimal sequencing to improve patient outcomes.

Recent advances in immunotherapy for small cell lung cancer.

This review aims to provide an overview of recent advances in immunotherapy for small cell lung cancer (SCLC), with a focus on the current status of immune checkpoint inhibitors (ICIs), novel combination strategies, and key biomarkers. The integration of ICIs into standard chemotherapy has established them as the first-line treatment for extensive-stage SCLC (ES-SCLC). The ADRIATIC trial further demonstrated the efficacy of ICI maintenance therapy in limited-stage SCLC. Additionally, combining radiotherapy with ICIs has shown promising synergistic effects, including the abscopal and radscopal effects. Ongoing investigations into the combination of ICIs with targeted therapies, such as antiangiogenic agents and DNA damage response inhibitors, have yielded encouraging preliminary results. Notably, the novel therapeutic agent tarlatamab, the first bispecific DLL3-directed CD3 T-cell engager, has recently received FDA approval for second-line treatment of ES-SCLC. Advances in omics technologies have shed light on the intra-tumor and inter-tumor heterogeneity of SCLC, leading to the identification of new molecular subtypes and biomarkers, thereby paving the way for precision medicine. Despite the improved outcomes associated with immunotherapy in SCLC, the overall clinical benefit remains modest. Further preclinical and clinical studies are essential to identify optimal treatment regimens and enhance therapeutic efficacy.

Immunotherapy for gastric cancer: Advances and challenges

AbstractGastric cancer (GC) ranks among the leading causes of cancer‐related mortality globally. Often, its initial stages manifest subtly, and the infrequency of routine screenings contributes to late diagnoses in many cases. Systemic treatments for GC include chemotherapy, targeted therapy, and immunotherapy, among which immunotherapy is the first‐line standard treatment for advanced GC. In recent years, immunotherapy has seen notable advancements, as evidenced by the Food and Drug Administration's approval of drugs such as nivolumab and pembrolizumab for GC treatment. Additionally, several other drugs are currently under rigorous preclinical and clinical investigation. This review aims to shed light on the recent advancements in immunotherapy for GC, particularly emphasizing the insights gained from phase 2/3 clinical trials that assess the efficacy, safety, and promise of various immunotherapeutic modalities, including immune checkpoint inhibitors, CAR‐T‐cell therapies, and cancer vaccines, in enhancing patient outcomes. Moreover, this review delves into the intricate immunological framework of GC, focusing on the tumor microenvironment, interactions among immune cells, and the roles of immune checkpoints such as PD‐L1. We also address the hurdles and prospective paths forward in the realm of immunotherapy for GC, offering fresh viewpoints on potential therapeutic approaches in this evolving domain.

Cancer of Unknown Primary Site: A New Era of Practice-Changing Approaches to Diagnosis, Staging, and Precision Therapy

The enigmatic syndrome of metastatic cancer of unknown primary (CUP) site has frustrated physicians and patients for decades. There has been debate whether CUP is a single biologically distinct cancer or a constellation of many different cancers with clinically undetectable anatomic primary sites. For the past 40 years, the diagnosis of a specific cancer type for most patients was indeterminate, and fit patients were usually treated as a single cancer with the same empiric chemotherapy (EC) regimens with poor overall results. The aggregate data from autopsies, clinical observations, specialized standard pathology, molecular testing, and several clinical trials support CUP as a multitude of clinically occult invasive primary tumors requiring different site-specific therapies (SSTs). In the past several years, improved genomic testing has been used, and the addition of molecular-guided therapies (MGTs) and immunotherapy (IO) has been shown to be superior for many different advanced cancers. Two older randomized prospective trials conducted before the advent of IO and most MGT failed to show a better outcome for patients with molecularly diagnosed cancers who received SST (tailored chemotherapy regimens) versus EC, although patients with more responsive tumor types appeared to benefit. Two recently reported randomized trials documented the clinical relevance of molecular diagnosis and comprehensive genomic profiling. The administration of improved precision SST guided by molecular diagnosis and characterization revealed significantly improved outcomes compared with EC. The management of patients with CUP is undergoing rapid change including the diagnosis of the presumed primary tumors, TNM staging for selected patients, molecular profiling, and an expanded improved role of precision therapies highlighting the rapid emergent new era of practice changing standards of care.

Disparities in Receipt of Adjuvant Immunotherapy among Stage III Melanoma Patients.

Melanoma survival has greatly improved with the advent of immunotherapy, but unequal access to these medications may exist due to nonmedical patient factors such as insurance status, educational background, and geographic proximity to treatment. We used the National Cancer Database to assess patients with nonmetastatic cutaneous melanoma who underwent surgical resection and sentinel lymph node biopsy (SLNB) with tumor involvement from 2015 to 2020. We evaluated rates of adjuvant immunotherapy among this patient population based on patient, tumor, and facility variables, including insurance status, socioeconomic status, pathologic stage (IIIA-IIID), and treatment facility type and volume. Adjuvant immunotherapy was associated with improved survival for stage III melanoma, with a slight increase in 5-year OS for stage IIIA (87.9% vs. 85.9%, P=0.044) and a higher increase in stages IIIB-D disease (70.3% vs. 59.6%, P<0.001). Receipt of adjuvant immunotherapy was less likely for patients who were older, low socioeconomic status, or uninsured. Low-volume and community cancer centers had higher rates of adjuvant immunotherapy overall for all stage III patients, whereas high-volume and academic centers used adjuvant immunotherapy much less often for stage IIIA patients compared with those in stages IIIB-D. Our results demonstrate inconsistent use of adjuvant immunotherapy among patients with stage III melanoma despite a significant association with improved survival. Notably, there was a lower use of adjuvant immunotherapy in patients of lower SES and those treated at high-volume centers. Equity in access to novel standards of care represents an opportunity to improve outcomes for patients with melanoma.

Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study.

Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors. Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high. The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control. Here, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors. NCT04510129.

Phase II Trial of Enfortumab Vedotin in Patients With Previously Treated Advanced Head and Neck Cancer.

Despite advances in immunotherapy, unresectable recurrent/metastatic head and neck cancer (HNC) carries a poor prognosis, and effective treatments are needed. As nectin-4 is widely expressed in HNC, enfortumab vedotin (EV), a nectin-4-directed antibody-drug conjugate, was explored in HNC in EV-202 (ClinicalTrials.gov identifier: NCT04225117). This open-label, multicohort, phase II study evaluated intravenous EV 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle. In the HNC cohort, eligible patients had recurrent/metastatic HNC and had received platinum-based therapy for locally advanced/metastatic disease and a PD-1/PD-L1 inhibitor. The primary end point was investigator-assessed confirmed objective response rate (ORR) per RECIST version 1.1. Secondary end points were investigator-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); overall survival (OS); and safety. The primary analysis included 46 patients; all received EV (median follow-up, 9.3 months). Most patients (52.2%) had ≥3 previous lines of systemic therapy in the metastatic setting. Confirmed ORR was 23.9%, DCR was 56.5%, and median DOR was not reached (median DOR was 9.4 months at a later data cutoff [median follow-up, 11.3 months]). Median PFS and OS were 3.9 and 6.0 months, respectively. Treatment-related adverse events (TRAEs) occurring in >20% of patients were alopecia (28.3%), fatigue (26.1%), and peripheral sensory neuropathy (23.9%). Sixteen patients (34.8%) experienced grade ≥3 TRAEs; anemia and decreased neutrophil count occurred in ≥1 patient (both n = 2; 4.3%). EV demonstrated antitumor activity in heavily pretreated HNC. Safety was consistent with the known safety profile of EV; no new safety signals were identified. These data support further evaluation of EV for advanced HNC not amenable to definitive local therapy.

Next-Generation Immunotherapy: Advancing Clinical Applications in Cancer Treatment.

Next-generation immunotherapies have revolutionized cancer treatment, offering hope for patients with hard-to-treat tumors. This review focuses on the clinical applications and advancements of key immune-based therapies, including immune checkpoint inhibitors, CAR-T cell therapy, and new cancer vaccines designed to harness the immune system to combat malignancies. A prime example is the success of pembrolizumab in the treatment of advanced melanoma, underscoring the transformative impact of these therapies. Combination treatments, integrating immunotherapy with chemotherapy, radiation, and targeted therapies, are demonstrating synergistic benefits and improving patient outcomes. This review also explores the evolving role of personalized immunotherapy, guided by biomarkers, genomic data, and the tumor environment, to better target individual tumors. Although significant progress has been made, challenges such as resistance, side effects, and high treatment costs persist. Technological innovations, including nanotechnology and artificial intelligence, are explored as future enablers of these therapies. The review evaluates key clinical trials, breakthroughs, and the emerging immune-modulating agents and advanced delivery systems that hold great promise for enhancing treatment efficacy, reducing toxicity, and expanding access to immunotherapy. In conclusion, this review highlights the ongoing advancements in immunotherapy that are reshaping cancer care, with future strategies poised to overcome current challenges and further extend therapeutic reach.

A single-cell perspective on immunotherapy for pancreatic cancer: from microenvironment analysis to therapeutic strategy innovation.

Pancreatic cancer remains one of the most lethal malignancies, with conventional treatment options providing limited efficacy. Recent advancements in immunotherapy have offered new hope, yet the unique tumor microenvironment (TME) of pancreatic cancer poses significant challenges to its successful application. This review explores the transformative impact of single-cell technology on the understanding and treatment of pancreatic cancer. By enabling high-resolution analysis of cellular heterogeneity within the TME, single-cell approaches have elucidated the complex interplay between various immune and tumor cell populations. These insights have led to the identification of predictive biomarkers and the development of innovative, personalized immunotherapeutic strategies. The review discusses the role of single-cell technology in dissecting the intricate immune landscape of pancreatic cancer, highlighting the discovery of T cell exhaustion profiles and macrophage polarization states that influence treatment response. Moreover, it outlines the potential of single-cell data in guiding the selection of immunotherapy drugs and optimizing treatment plans. The review also addresses the challenges and prospects of translating these single-cell-based innovations into clinical practice, emphasizing the need for interdisciplinary research and the integration of artificial intelligence to overcome current limitations. Ultimately, the review underscores the promise of single-cell technology in driving therapeutic strategy innovation and improving patient outcomes in the battle against pancreatic cancer.

Recent Advances in the Translational Application of Immunotherapy with Pulsed Dendritic Cell-Derived Exosomes (DEX)

This article explores recent advances in immunotherapy using exosomes derived from dendritic cells (DEXs), highlighting their potential as an innovative option in cancer treatment. DEXs have demonstrated the ability to activate robust and sustainable immune responses, overcoming the limitations of conventional therapies. Their low toxicity profile and capacity to induce long-term immunological memory position them as a viable alternative, especially for patients who do not respond to traditional treatments. The article analyzes the mechanisms of action of DEXs and details their optimized production using advanced pulsing techniques. Clinical trials in melanoma, lung cancer, and other resistant tumors underscore their efficacy and the potential for combining them with conventional treatments, thereby improving tolerance and increasing effectiveness by minimizing adverse reactions. Additionally, the article reviews the epicutaneous administration of DEXs, a strategy that enhances immune response while improving patient experience. The adaptability of DEXs to different types and stages of cancer makes them a fundamental tool in personalized oncology. The question is no longer whether this therapy is effective, but rather when and which low-cost implementation option will be chosen for clinical use, consolidating DEXs as an innovative and validated therapeutic line integrated into protocols that promote more precise and safer treatments with greater effectiveness.