Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides

Tjoa, Benjamin A.; Simmons, S.J.; Bowes, Victoria; Ragde, Haakon; Rogers, M.; Elgamal, Abdel-Aziz A.; Kenny, Gerald M.; Cobb, Oliver E.; Ireton, Robert C.; Troychak, M.J.; Salgaller, Michael L.; Boynton, Alton L.; Murphy, Gerald P.

doi:10.1002/(sici)1097-0045(19980615)36:1<39::aid-pros6>3.0.co;2-6

Cited by 219 publications

(84 citation statements)

References 8 publications

(3 reference statements)

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“…27 In an earlier study, objective clinical remissions were observed after vaccination with DC loaded with HLA-A2-restricted PSMA-derived peptide-even in HLA-A2 negative patients. 36 In 2 other studies, vaccination with DC-enriched PBMC loaded with a prostatic acid phosphatase (PAP)/GM-CSF fusion protein induced partial PSA responses in 3/31 and 3/12 patients. 8,37 Recombinant murine PAP loaded onto DC-enriched PBMC was able to elicit T-cell proliferative responses to human PAP and disease stabilization.…”

Section: Discussionmentioning

confidence: 99%

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

Thomas-Kaskel

Zeiser

Jochim

et al. 2006

Intl Journal of Cancer

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Prostate stem cell antigen (PSCA) and prostate‐specific antigen (PSA) are overexpressed in most prostate cancers. PSCA‐ and PSA‐derived, HLA‐A2 binding peptides are specific targets for T‐cell responses in vitro. A phase I/II trial was performed to demonstrate feasibility, safety and induction of antigen‐specific immunity by vaccination with dendritic cells (DC) presenting PSCA and PSA peptides in patients with hormone‐ and chemotherapy‐refractory prostate cancer. Patients received 4 vaccinations with a median of 2.7 × 107 peptide‐loaded mature DC s.c. in biweekly intervals. Clinical responses were assessed 2 weeks after the 4th vaccination. Immune monitoring was performed by DTH and HLA multimer analysis. Twelve patients completed vaccination without relevant toxicities. Six patients had stable disease after 4 vaccinations. One patient had a complete disappearance of lymphadenopathy despite rising PSA. Four patients with SD and 1 progressor developed a positive DTH after the 4th vaccination. With a median survival of all patients of 13.4 months, DTH‐positivity was associated with significantly superior survival (p = 0.003). HLA tetramer analysis detected high frequencies of peptide‐specific T cells after 2 vaccinations in 1 patient who was also the sole responder to concomitant hepatitis B vaccination as an indicator of immune competence and survived 27 months after start of vaccination. Vaccination with PSA/PSCA peptide‐loaded, autologous DCs may induce cellular responses primarily in immunocompetent patients, which appear to be associated with clinical benefit. Testing of DC‐based vaccination is warranted for patients at earlier stages of prostate cancer. © 2006 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

Thomas-Kaskel

Zeiser

Jochim

et al. 2006

Intl Journal of Cancer

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“…However, the appropriate conditioning of DCs to induce the most potent anticancer immune reaction in vivo is still unclear (18,19,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). One of the problems to be elucidated is how to obtain DCs that are capable of migrating into secondary lymphoid organs to prime T cells when injected.…”

Section: Discussionmentioning

confidence: 99%

The Duration of Signaling through CD40 Directs Biological Ability of Dendritic Cells to Induce Antitumor Immunity

Watanabe

Kagamu

Yoshizawa

et al. 2003

The Journal of Immunology

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Although it has been demonstrated that the functions of dendritic cells (DCs), including Ag capture, Ag presentation, and migratory activity, change dynamically with their maturation, the most appropriate conditioning of DCs for anticancer immunotherapy is still unclear. The help signal is one of the most potent stimuli for DC maturation and is provided by the interaction of CD40 expressed on DCs with CD40 ligand on CD4+ T cells. To elucidate the appropriate conditioning of DCs for anticancer immunotherapy, we examined the biological activity of DCs stimulated with immobilized anti-CD40 Ab. DCs stimulated for 3 h (3h-DCs) still showed an immature phenotype, but exhibited augmented migration toward secondary lymphoid tissues. Subcutaneous injection of 3h-DCs facilitated priming of T cells, which could mediate potent antitumor therapeutic efficacy, in draining lymph nodes and successfully induced protective immunity. In contrast, 24h-DCs showed a mature phenotype with good Ag presentation ability to induce cell killing by adoptively transferred CD8+ T cells when injected at tumor sites; however, they showed no migratory activity and were unable to induce protective immunity when injected s.c.. This is the first report that functionally distinct DCs, either for the priming phase or for the effector phase, could be obtained by conditioning with CD40 stimulation and that the duration of stimulation determines the biological outcome. The usage of DCs conditioned for the priming phase might provide significant advantages in anticancer immunotherapy.

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“…Murphy and Tjoa [160][161][162][163][164] have performed several phase I and II clinical trials of the use of PSMA-derived peptide-pulsed DC for patients with locally advanced or metastatic PC. They loaded monocyte-derived DC with one of two HLA-A2-restricted PSMA-derived peptides (PSM-P1 and PSM-P2), and administered them intravenously.…”

Section: Dc-based Pc Vaccinesmentioning

confidence: 99%

Immunology and immunotherapy approaches for prostate cancer

Elkord

2007

Prostate Cancer Prostatic Dis

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Several mechanisms that impair the immune response to promote tumour progression are reported. These mechanisms aim to reduce the ability of antigen-presenting cells to present antigen and activate naïve T cells to support an active immune response or to create a suppressive environment that induce non-functional tumour-associated antigen-specific T cells. Prostate cancer (PC) alone accounts for 33% of incident cancer cases and about 9% of all cancer-related deaths among men in the USA during 2006. Whereas androgen deprivation has remained the first line of therapy for advanced PC, other therapies are still required due to progression to an androgen-resistant state and eventually loss of control in patients receiving hormonal therapy. Immunotherapy seems to be a promising approach to enhance tumour-specific T-cell responses in different cancers including prostate. More importantly, clinical trials in advanced PC patients have shown that immunotherapy may generate significant clinical responses. Immunology and immunotherapy aspects of PC with focus on prostate-specific antigen will be presented.

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Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides

Cited by 219 publications

References 8 publications

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

Vaccination of advanced prostate cancer patients with PSCA and PSA peptide‐loaded dendritic cells induces DTH responses that correlate with superior overall survival

The Duration of Signaling through CD40 Directs Biological Ability of Dendritic Cells to Induce Antitumor Immunity

Immunology and immunotherapy approaches for prostate cancer

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