Prostate Cancer Vaccine Research Articles

1023P Long-term follow up of patients treated with a DNA vaccine (pTVG-HP) for PSA-recurrent prostate cancer

1023P Long-term follow up of patients treated with a DNA vaccine (pTVG-HP) for PSA-recurrent prostate cancer

Sequence of androgen receptor-targeted vaccination with androgen deprivation therapy affects anti-prostate tumor efficacy

RationaleAndrogen deprivation therapy (ADT) is the primary treatment for recurrent and metastatic prostate cancer. In addition to direct antitumor effects, ADT has immunomodulatory effects such as promoting T-cell infiltration and...

Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis.

Human Embryonic Kidney cells (HEK293) are a popular host for recombinant protein expression and production in the biotechnological industry. This has driven within both, the scientific and the engineering communities, the search for strategies to increase their protein productivity. The present work is inserted into this search exploring the impact of adding sodium acetate (NaAc) into a batch culture of HEK293 cells. We monitored, as a function of time, the cell density, many external metabolites, and the supernatant concentration of the heterologous extra-cellular domain ECD-Her1 protein, a protein used to produce a candidate prostate cancer vaccine. We observed that by adding different concentrations of NaAc (0, 4, 6 and 8mM), the production of ECD-Her1 protein increases consistently with increasing concentration, whereas the carrying capacity of the medium decreases. To understand these results we exploited a combination of experimental and computational techniques. Metabolic Flux Analysis (MFA) was used to infer intracellular metabolic fluxes from the concentration of external metabolites. Moreover, we measured independently the extracellular acidification rate and oxygen consumption rate of the cells. Both approaches support the idea that the addition of NaAc to the culture has a significant impact on the metabolism of the HEK293 cells and that, if properly tuned, enhances the productivity of the heterologous ECD-Her1 protein.

A Review of Clinical Trials of Cancer and Its Treatment as a Vaccine.

Cancer and infectious diseases are one of the greatest challenges of modern medicine. An unhealthy lifestyle, poor drug use, or drug misuse contribute to the rise in morbidity and mortality brought on by these illnesses. The inadequacies of the medications now being used to treat these disorders, along with the growing issue of drug resistance, have compelled researchers to look for novel compounds with therapeutic promise. The number of infections and diseases has significantly abated due to vaccine development and use over time, which is described in detail. Several novel vaccines can now be produced by manipulating Deoxyribonucleic acid (DNA), Ribonucleic acid (RNA), Messenger Ribonucleic acid (mRNA), proteins, viral vector Recombinant, and other molecules due to advances in genetic engineering and our understanding of the immune defense. The main topic of discussion is cancer-based vaccinations, which were developed less than a decade ago but have already been used to treat a wide range of both life-threatening and deadly diseases. It contains clinical studies for cancer vaccines against kidney, liver, prostate, cervix, and certain RNA-based cancer vaccines against breast and bladder cancer. Numerous studies using various DNA and RNA-based methods have been conducted on the basis of cancer, with 9-10 diseases related to DNA and 8-9 diseases associated with RNA. Some of these studies have been completed, while others have been eliminated due to a lack of research; further studies are ongoing regarding the same. This brief discussion of vaccines and their varieties with examples also discusses vaccine clinical trials in relation to cancer diseases in this DNA and RNA-based cancer vaccine that has had successful clinical trials like the cervical cancer drug VGX-3100, the kidney cancer drug Pembrolizumab, MGN-1601, the prostate cancer drug pTVG-HP with rhGM-CSF, the melanoma cancer drug proteasome siRNA, and the lung cancer drug FRAME-001.

The Up to Date Progress of Prostate Cancer Vaccines

The prostate cancer vaccine has significant influences on males, and the cancer among American men has second highest prevalence among all cancers. Both the prevalence and mortality rates of prostate cancer in America are increasing each year. Researchers have been working to improve and innovate the way prostate cancer is diagnosed and treated. One promising direction is immunotherapy. Scientists have been working on a vaccine for prostate cancer for decades, and FDA only passes Sipuleucel-T as prostate cancer vaccine, but many other prostate cancer vaccines have been developed. Therefore, after synthesizing many papers, this paper explains the principles, latest progress, the advantages and disadvantages of all the vaccines developed so far, and proposes that future researchers should improve the prostate cancer vaccine in the direction of combination therapy, and conduct in-depth research to explore the prostate cancer vaccines that are currently showing an excellent trend, and to optimize the Sipuleucel-T.

Prevalence and determinants of community members utilizing preventive services offered by family physicians in Riyadh, Saudi Arabia.

Early detection and prevention of diseases can reduce morbidity, mortality, and economic burden. There is need to assess the utilization of preventive services for common chronic diseases, cancers, and vaccinations. This study aimed to estimate the prevalence and sequence of utilization of preventive services for common chronic diseases, cancers, and vaccinations in addition to exploring community perspectives on these services. This study was a cross-sectional survey, which was conducted at primary healthcare centers in Prince Sultan Military Medical City covering Riyadh region from October 2022 to January 2023. The study used a self-administered questionnaire to collect data from attendees aged 18 years and older, focusing on the utilization of eight preventive services (blood glucose testing, blood pressure measurement, cholesterol testing, screening for breast cancer, screening for cervical cancer, screening for colorectal cancer, screening for prostate cancer, and flu and pneumococcal vaccines). Descriptive statistics of the study were reported in frequencies and percentages. Chi-square test was used to assess association between outcome variables. Participants were mostly married and had a higher educational degree. However, a considerable number is not accessing primary healthcare services regularly. The results showed that the rate of utilizing preventive services was as follows: blood pressure screening (91%), blood glucose testing (72%), cholesterol testing (65.8%), vaccination utilization (39.5%), breast cancer screening (8%), prostate cancer screening (4.6%), colon cancer screening (4.2%), and least utilized was cervical cancer screening with frequency of (3%). The results underscore the importance of increasing awareness and accessibility of primary healthcare services to promote better health outcomes in the region.

Co-transient expression of PSA-Fc and PAP-Fc fusion protein in plant as prostate cancer vaccine candidates and immune responses in mice.

PAP-FcK and PSA-FcK prostate cancer antigenic proteins transiently co-expressed in plant induce their specific humoral immune responses in mice. Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been considered as immunotherapeutic antigens for prostate cancer. The use of a single antigenic agent is unlikely to be effective in eliciting immunotherapeutic responses due to the heterogeneous and multifocal nature of prostate cancer. Thus, multiple antigens have been combined to enhance their anti-cancer effects. In the current study, PSA and PAP were fused to the crystallizable region (Fc region) of immunoglobulin G1 and tagged with KDEL, the endoplasmic reticulum (ER) retention signal motif, to generate PSA-FcK and PAP-FcK, respectively, and were transiently co-expressed in Nicotiana benthamiana. Western blot analysis confirmed the co-expression of PSA-FcK and PAP-FcK (PSA-FcK + PAP-FcK) with a 1:3 ratios in the co-infiltrated plants. PSA-FcK, PAP-FcK, and PSA-FcK + PAP-FcK proteins were successfully purified from N. benthamiana by protein A affinity chromatography. ELISA showed that anti-PAP and anti-PSA antibodies successfully detected PAP-FcK and PSA-FcK, respectively, and both detected PSA-FcK + PAP-FcK. Surface plasmon resonance (SPR) analysis confirmed the binding affinity of the plant-derived Fc fusion proteins to FcγRI/CD64. Furthermore, we also confirmed that mice injected with PSA-FcK + PAP-FcK produced both PSA- and PAP-specific IgGs, demonstrating their immunogenicity. This study suggested that the transient plant expression system can be applied to produce the dual-antigen Fc fusion protein (PSA-FcK + PAP-FcK) for prostate cancer immunotherapy.

Androgen receptor–specific CD8+ T cells with tumor cell cytotoxicity in patients with prostate cancer in Taiwan.

e17069 Background: Classical androgen receptor (AR) target is the new “tumor-specific” antigen for prostate cancer vaccine development to delay progression and castration-resistant disease. HLA-A2-restricted AR ligand-binding domain (LBD) has been demonstrated to stimulate cytotoxic T lymphocytes (CTL) in HLA-A2+ prostate cancer patients. Although the prevalence of HLA-A2 serotype and LBD-specific CD8+ T cells among Caucasians are known, their frequencies in the Taiwan patients have not been established. In this study, we performed HLA-A2 genotyping, HLA-A2+ LNCaP stimulation of autologous T cell, and CTL tumor cell cytotoxicity from 25 castration-sensitive prostate cancer patients using blood samples collected from a single hospital center. Methods: 20ml whole blood samples are collected in EDTA tube from non-metastatic, castration-sensitive prostate cancer patients. PBMCs are subjected to HLA-A2 allele sequencing, separated by CD3 magnetic bead column, and expanded and activated ex vivo using CD3/CD8 polymeric beads. Autologous T cells are then isolated by CD8 magnetic bead column, stimulated by HLA-A2+ lentivirus-transduced LNCaP (AR+), and targeted against transduced (HLA-A2+) and non-transduced (HLA-A2-) LNCaP (AR+) by Chromium-51 Release Assay. We identified and correlated their frequencies with patient’s age at diagnosis, Gleason grades, PSA level, and family history. Results: A total of 25 blood samples were tested and analyzed for HLA-A2 genotype with 44% (11/25) positive for the HLA-A2 [28% (7/25) heterozygotes, 16% (4/25) homozygotes]. Among the 11 HLA-A2+ patients, 72% (8/11) were HLA-A*02:07 allele, 100% (11/11) CD8+ T cells were successfully stimulated with HLA-A2+ transduced LNCaP (AR+) and 45% (5/11) patients demonstrated HLA-A2+ AR-specific CTL tumor cell lysis. No clinical association with patient age (54-86 y.o.), Gleason grades (6-9), PSA level (3.84-62.8 ng/ml), and family history (1/25). Conclusions: In this single hospital center study, we observed a similar prevalence of HLA-A2 alleles in Taiwan prostate cancer patient cohort with a predominant HLA-A2*02:07 allele, and higher frequencies of HLA-A2-restricted CD8+ T cell stimulation and HLA-A2+ AR-specific tumor cell cytotoxicity. Our findings support the application of AR LBD as tumor antigen for prostate cancer vaccine development for Taiwan prostate cancer patients.

Advances in Immunotherapy and Vaccine for Prostate Cancer

Prostate cancer is one of the most common malignant tumors of the urinary system. The incidence of prostate cancer is high in the elderly male patients, which seriously threatens the life and health. In recent years, immunotherapy to activate anti-cancer host immune cells to kill tumors has become a new area of research for the treatment of prostate cancer. As an important component of immunotherapy, cancer vaccines have a unique position in the precise treatment of malignant tumors. There are many types of prostate cancer vaccines, including monocyte vaccines, dendritic cell vaccines, viral vaccines, peptide vaccines, and DNA/mRNA vaccines, etc. As the most important cancer vaccine based on monocytes, it is the only prostate cancer therapeutic vaccine approved by the US Food and Drug Administration at present, which plays an extremely important role in the immunotherapy of prostate cancer. However, due to its own limitations, SipuleucelT has not been widely adopted. Currently, the complexity of immunotherapy and the specificity of prostate cancer mean that other prostate cancer vaccines have not shown expected clinical benefits in large randomized phase II and III trials, and further in-depth studies are still needed.

Plant-derived PAP proteins fused to immunoglobulin A and M Fc domains induce anti-prostate cancer immune response in mice

In this study, recombinant Fc-fused Prostate acid phosphatase (PAP) proteins were produced in transgenic plants. PAP was fused to immunoglobulin (Ig) A and M Fc domain (PAP-IgA Fc and PAP-IgM Fc), which were tagged to the ER retention sequence KDEL to generate PAP-IgA FcK and PAP-IgM FcK. Agrobacterium-meditated transformation was performed to produce transgenic tobacco plants expressing four recombinant proteins. Genomic PCR and RT-PCR analyses confirmed the transgene insertion and mRNA transcription of PAP-IgA Fc, PAP-IgM Fc, PAP-IgA FcK, and PAP-IgM FcK in tobacco plant leaves. Western blot confirmed the expression of PAP-IgA Fc, PAP-IgM Fc, PAP-IgA FcK, and PAP-IgM FcK proteins. SEC-HPLC and Bio-TEM analyses were performed to confirm the size and shape of the plant-derived recombinant PAP-Fc fusion proteins. In mice experiments, the plant-derived IgA and IgM Fc fused proteins induced production of total IgGs including IgG1 against PAP. This result suggests that IgA and IgM Fc fusion can be applied to produce recombinant PAP proteins as a prostate cancer vaccine in plant expression system.

Vaccines as treatments for prostate cancer.

Prostate cancer is a leading cause of death in men worldwide. For over 30 years, growing interest has focused on the development of vaccines as treatments for prostate cancer, with the goal of using vaccines to activate immune cells capable of targeting prostate cancer to either eradicate recurrent disease or at least delay disease progression. This interest has been prompted by the prevalence and long natural history of the disease and by the fact that the prostate is an expendable organ. Thus, an immune response elicited by vaccination might not need to target the tumour uniquely but could theoretically target any prostate tissue. To date, different vaccine approaches and targets for prostate cancer have been evaluated in clinical trials. Overall, five approaches have been assessed in randomized phase III trials and sipuleucel-T was approved as a treatment for metastaticcastration-resistant prostate cancer, being the only vaccine approved to date by the FDA as a treatment for cancer. Most vaccine approaches showed safety and some evidence of immunological activity but had poor clinical activity when used as monotherapies. However, increased activity has been observed when these vaccines were used in combination with other immune-modulating therapies. This evidence suggests that, in the future, prostate cancer vaccines might be used to activate and expand tumour-specific T cells as part of combination approacheswith agents that target tumour-associated immune mechanisms of resistance.

19 - Phase I study of in-situ autologous vaccination for prostate cancer in a neo-adjuvant setting

19 - Phase I study of in-situ autologous vaccination for prostate cancer in a neo-adjuvant setting

Advances in cancer vaccines for immunotherapy of prostate cancer.

Prostate cancer is currently one of the most common malignancies that endanger the lives and health of elderly men. In recent years, immunotherapy, which exploits the activation of anti-cancer host immune cells to accomplish tumor-killing effects, has emerged as a new study avenue in the treatment of prostate cancer. As an important component of immunotherapy, cancer vaccines have a unique position in the precision treatment of malignant tumors. Monocyte cell vaccines, dendritic cell vaccines, viral vaccines, peptide vaccines, and DNA/mRNA vaccines are the most often used prostate cancer vaccines. Among them, Sipuleucel-T, as a monocyte cell-based cancer vaccine, is the only FDA-approved therapeutic vaccine for prostate cancer, and has a unique position and role in advancing the development of immunotherapy for prostate cancer. However, due to its own limitations, Sipuleucel-T has not been widely adopted. Meanwhile, owing to the complexity of immunotherapy and the specificity of prostate cancer, the remaining prostate cancer vaccines have not shown good clinical benefit in large randomized phase II and phase III trials, and further in-depth studies are still needed.

Current status and progress of the development of prostate cancer vaccines.

At present, common treatments of prostate cancer mainly include surgery, radiotherapy, chemotherapy and hormone therapy. However, patients have high recurrence rate after treatment, and are prone to castration-resistant prostate cancer. Tumor vaccine is based on tumor specific antigen (TSA) and tumor associated antigen (TAA) to activate specific immune response of the body to cancer cells. With continuous maturity of tumor vaccine technology, different forms of prostate cancer vaccines have been developed, such as cellular vaccines, extracellular-based anti-tumor vaccines, polypeptide vaccines, and nucleic acid vaccines. In this review, we summarize current status and progress in the development of prostate cancer vaccines.

A Phase 2, Double-blind, Randomized Controlled Trial of PROSTVAC in Prostate Cancer Patients on Active Surveillance

BackgroundThere is an unmet clinical need for interventions to prevent disease progression in patients with localized prostate cancer on active surveillance (AS). ObjectiveTo determine the immunologic response to the PROSTVAC vaccine and the clinical indicators of disease progression in patients with localized prostate cancer on AS. Design, setting, and participantsThis was a phase 2, double-blind, randomized controlled trial in 154 men with low- or intermediate-risk prostate cancer on AS. InterventionParticipants were randomized (2:1) to receive seven doses of subcutaneous PROSTVAC, a vaccinia/fowlpox viral vector–based immunotherapy containing a prostate-specific antigen (PSA) transgene and three T-cell co-stimulatory molecules, or an empty fowlpox vector (EV) over 140 d. Outcome measurements and statistical analysisThe primary outcome was the change from baseline in CD4 and CD8 T-cell infiltration in biopsy tumor tissue. Key secondary outcomes were safety and changes in prostate biopsy tumor pathology, peripheral antigen-specific T cells, and serum PSA. Continuous variables were compared using nonparametric tests. Categorical variables were compared using Fisher’s exact test. Results and limitationsThe PROSTVAC/EV vaccination was well tolerated. All except one participant completed the vaccination series. Changes in CD4 or CD8 density in biopsy tumor tissue did not differ between the PROSTVAC and EV arms. The proportions of patients with Gleason upgrading to grade group 3 after treatment was similar between the arms. There were no differences in postvaccination peripheral T-cell responses or the PSA change from baseline to 6-mo post-treatment follow-up between the groups. ConclusionsIn this first-of-kind trial of immunotherapy in patients on AS for prostate cancer, PROSTVAC did not elicit more favorable prostate tissue or peripheral T-cell responses than the EV. There was no difference between the arms in clinicopathologic effects. Despite the null findings, this is the first study reporting the feasibility and acceptability of an immunotherapy intervention in the AS setting. Patient summaryWe looked at responses after an experimental prostate cancer vaccine in patients with prostate cancer on active surveillance (AS). Participants who received the vaccine did not show more favorable outcomes than those receiving the control. Despite these findings, this is the first report showing the feasibility and acceptability of immunotherapy for prostate cancer in patients on AS.

Peptide Modification Diminishes HLA Class II-restricted CD4+ T Cell Recognition of Prostate Cancer Cells

Prostate cancer poses an ongoing problem in the western world accounting for significant morbidity and mortality in the male population. Current therapy options are effective in treating most prostate cancer patients, but a significant number of patients progress beyond a manageable disease. For these patients, immunotherapy has emerged as a real option in the treatment of the late-stage metastatic disease. Unfortunately, even the most successful immunotherapy strategies have only led to a four-month increase in survival. One issue responsible for the shortcomings in cancer immunotherapy is the inability to stimulate helper CD4+ T cells via the HLA class II pathway to generate a potent antitumor response. Obstacles to proper HLA class II stimulation in prostate cancer vaccine design include the lack of detectable class II proteins in prostate tumors and the absence of defined class II specific prostate tumor antigens. Here, for the first time, we show that the insertion of a lysosomal thiol reductase (GILT) into prostate cancer cells directly enhances HLA class II antigen processing and results in increased CD4+ T cell activation by prostate cancer cells. We also show that GILT insertion does not alter the expression of prostate-specific membrane antigen (PSMA), an important target in prostate cancer vaccine strategies. Our study suggests that GILT expression enhances the presentation of the immunodominant PSMA459 epitope via the HLA class II pathway. Biochemical analysis showed that the PSMA459 peptide was cysteinylated under a normal physiologic concentration of cystine, and this cysteinylated form of PSMA459 inhibited T cell activation. Taken together, these results suggest that GILT has the potential to increase HLA class II Ag presentation and CD4+ T cell recognition of prostate cancer cells, and GILT-expressing prostate cancer cells could be used in designing cell therapy and/or vaccines against prostate cancer.

Intravenous administration of viral vectors expressing prostate cancer antigens enhances the magnitude and functionality of CD8+ T cell responses

BackgroundThe use of immunotherapeutic vaccination in prostate cancer is a promising approach that likely requires the induction of functional, cytotoxic T cells . The experimental approach described here uses a...

Cancer treatment vaccine: DNA vaccines in treating prostate cancer and colorectal cancer

Therapeutic DNA cancer vaccines are now widely regarded as a potential technique for stimulating the immune system's response to cancer. Several clinical experiments involving plasmid DNA vaccines have already the induction of a wide and targeted immune response. Unfortunately, due to the tumor's immunosuppressive mechanisms, these vaccinations often showed very modest therapeutic results in clinical trials. This paper looks at how DNA vaccines for prostate cancer are progressing, as well as colorectal cancer clinical trials. This paper also examines the rationale for various treatment combinations and antigen selection strategies being developed to circumvent the limits of the cancer DNA vaccine. This paper focuses on the most promising discoveries as well as major concerns that must be addressed before therapeutic cancer DNA vaccines may be approved as part of standard cancer care for prostate cancer and colorectal cancer.

Abstract 3556: Immunopeptidomics-guided tumor antigen warehouse design and first clinical application of a personalized peptide vaccine for prostate cancer

Abstract Prostate cancer is the second most common malignancy in men with radical prostatectomy and radio-therapy being the primary curative treatment modalities in localized disease. However, up to 30% of patients experience recurrence that frequently leads to the development of metastatic disease associated with poor outcome. Therefore, novel, effective and low-side effect treatment options are essential, in particular for elderly and frail prostate cancer patients not eligible for intense therapy. Whereas, immune checkpoint inhibitors showed limited efficacy in prostate cancer so far, targeted T cell-based approaches with bispecific antibodies and cancer vaccines achieved promising results in this tumor entity. In this study, we established a prostate-associated off-the-shelf peptide warehouse, using mass-spectrometry-based immunopeptidome analysis of a large cohort of primary prostate tissue (n = 51), for the development of a broadly applicable personalized vaccine. The prostate dataset (23 prostate cancer, 12 adjacent benign, 16 benign prostate samples) comprising 29,893 HLA class I and II molecules, was compared to the immunopeptidomes of various benign non-prostate tissues (HLA-Ligand Atlas) to identify prostate exclusive antigens. Further antigen selection was based on the high presentation frequency. In total, 30 frequently expressed and prostate exclusive HLA class I peptides restricted to the six common allotypes HLA-A*02, -A*03, -A*24, -B*07, -B*08 and -B*40, covering more than 76% of the world population for at least one allotype, and five promiscuous HLA-DR restricted peptides found in up to 37% of prostates were selected. Immunogenicity was validated by IFNγ ELISPOT screening for preexisting T cell responses, as well as by in vitro priming experiments of naïve T cells in prostate cancer patients and healthy volunteers. The peptide warehouse will enable the formulation of personalized vaccines based on individual HLA allotype and immunopeptidome analysis of patient’s tumor samples in a reasonable time and cost frame within large cohort studies. We provided first evidence for the feasibility of this approach by designing a personalized immunopeptidome-guided peptide vaccine for a patient with metastatic prostate cancer. The vaccine was adjuvanted with the toll-like receptor 1/2 agonist XS15 emulsified in Montanide࣪ ISA51 VG and applied three times within a 12-week interval. Induction of a profound T cell response targeting 7/9 (78%) vaccine peptides was observed one week after the second vaccination. T cell responses have been persisting for almost two years in the patient, and in combination with androgen deprivation therapy enabled persistent PSA remission. In conclusion, we designed an immunopeptidomics-guided peptide warehouse and provided first evidence for its personalized application in prostate cancer patients. Citation Format: Yacine Maringer, Lena Freudenmann, Annika Nelde, Jonas S. Heitmann, Helmut R. Salih, Marissa Dubbelaar, Jörg Hennenlotter, Arnulf Stenzl, Jens Bedke, Hans-Georg Rammensee, Juliane S. Walz. Immunopeptidomics-guided tumor antigen warehouse design and first clinical application of a personalized peptide vaccine for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3556.

Abstract 4160: Promoting immunogenicity of synthetic long peptide vaccines based on in vivo IgG complex formation: Preclinical evaluation and clinical entry of the TET platform

Abstract Vaccines based on synthetic long peptides, targeting immunogenic region(s) of tumor associated proteins, are becoming increasingly used in oncology. Synthetic long peptides require endogenous processing by antigen presenting cells to be presented to T cells, thus reducing the risk of antigen presentation by non-professional antigen presenting cells lacking co-stimulation receptors. The formulation and delivery strategies require further development as peptides degrade rapidly in vivo. Herein we make use of a novel targeting and adjuvant strategy to deliver peptides to antigen presenting cells. Tumor-derived peptides are coupled to a B cell epitope element (the MTTE sequence, a tetanus toxin-derived universal B cell epitope) which induce the formation of peptide-conjugate -complex formation in vivo. This strategy, further named the TET technology, makes use of pre-existing antibodies to improve the bioavailability, stability, and immunogenicity of tumor-derived peptide therapeutics. The TET technology is here used in TENDU, a first-in-class prostate cancer vaccine candidate. TENDU incorporates selected immunogenic prostate cancer epitopes derived from PAP and PSMA. The peptides are designed to include proteasome processing elements along with a unique TAP translocation element. To assess the design, a conjugate with a known DR4 epitope embedded in a longer peptide was evaluated for T cell priming in HLA-DR4 animals and displayed T cell expansion in response to a prime/boost vaccination. To ensure that prostate cancer patients respond with antibodies to the MTTE sequence after a tetanus toxoid (TTd) vaccination, both healthy controls and patients (age and gender matched) were vaccinated using a TTd-based vaccine regime. Anti-MTTE antibody titers were evaluated. Patients and HCs responded with increased IgG1 type antibodies against MTTE after TTd vaccination. Safety with regards to hypersensitivity in response to the vaccine platform was evaluated in rabbits and a human whole blood loop system without any identified adverse events. Based on preclinical data the no-observed-adverse-effect level (NOAEL) was set to 1440µg/dose. The vaccine is currently assessed in a First-in-Human clinical study (TENDU-101, 3+3 study design) in patients with relapse after a primary radical prostatectomy. No safety concerns were noted at the lowest dose level and the 400 µg dose cohort has been initiated with the first patient dosed with no reported adverse events. The study’s primary endpoints are safety and tolerability. Secondary endpoints involve cellular immune responses, systemic PSA and PAP levels along with dose level selection. In conclusion, TENDU, a first-in-class vaccine candidate is under clinical development evaluating safety and tolerability for the TET vaccine platform technology. Citation Format: Erika Fletcher, Iliana Kerzeli, Robert Cordfunke, Aikaterini Nasi, Gunilla Törnqvist, Robert Valentijn, Frida Lindqvist, Inken Dillmann, Martin Lord, Neanke Bouwman, Jacques Neefjes, Natasja Dolezal, Kees Franken, Stephanie McArdle, Murrium Ahmad, Silvia Johansson, Ferry Ossendorp, Michael Haggman, Wolfgang Lilleby, Gustav Ullenhag, Sam Ladjevardi, Justyna Jarblad, Jan Wouter Drijfhout, Sara Mangsbo. Promoting immunogenicity of synthetic long peptide vaccines based on in vivo IgG complex formation: Preclinical evaluation and clinical entry of the TET platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4160.