In Vitro Generation of Human Cytotoxic T Lymphocytes Specific for Peptides Derived From Prostate-Specific Antigen

Correale, Pierpaolo; Walmsley, Konstantin; Nieroda, Carol; Zaremba, Sam; Zhu, Mingzhu; Schlom, Jeffrey; Tsang, Kwong Y.

doi:10.1093/jnci/89.4.293

Cited by 229 publications

(138 citation statements)

References 31 publications

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“…Neither the MUC-1-specific nor the PSA-specific T-cell line lysed the melanoma line, which is negative for both PSA and MUC-1. Previous studies (10,38) have shown that the CD8 + T-cell lines generated by both PSA and MUC-1 peptides employed here are MHC restricted.…”

Section: Resultsmentioning

confidence: 87%

“…Theses included the generation of T cells directed against PSMA, PAP, PSCA, and/or MUC-1 ( In light of the ELISPOT results in which we observed generation of a T-cell response postvaccination to both PSA and MUC-1, we conducted studies to determine if we can generate T-cell lines from the postvaccination PBMCs that were specific for either PSA or MUC-1 epitopes. The 10-mer PSA and MUC-1 peptides used have been described previously (10,38). Autologous dendritic cells were pulsed with PSA or MUC-1 peptide to generate T cells from PBMC as described in Materials and Methods.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, it has been shown that T cells stimulated to recognize PSA can specifically kill PSA-expressing tumor cells (9,10) and that these PSA-based vaccines are well tolerated with no doselimiting toxicities noted (12 -14). It has also been shown in both preclinical studies (15) and clinical studies (16,17) that a primary vaccination with rV followed by multiple boosting vaccinations with recombinant avipox vaccine is superior to the reciprocal regimen or the continued use of one vaccine.…”

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confidence: 99%

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Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer

Gulley¹,

Arlen²,

Bastian³

et al. 2005

Clinical Cancer Research

338

249

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Purpose: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. Experimental Design:We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapyonly arms. Those patients in the combination arm received a ''priming'' vaccine with recombinant vaccinia (r V) PSA plus r V containing theT-cell costimulatory molecule B7.1 (r V-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor andlow-dose systemicinterleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. Results: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specificTcells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P <0.0005).There was also evidence ofde novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. Conclusion:This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer

Gulley¹,

Arlen²,

Bastian³

et al. 2005

Clinical Cancer Research

338

249

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“…Nevertheless, the choice of the different monitoring tools is a matter of constant debate (Keilholz et al, 2002;Coulie and van der Bruggen, 2003). Although HLA A2-restricted PSA-derived peptides have been identified (Correale et al, 1997;Chakraborty et al, 2003), the use of peptides for immunological monitoring significantly limits the number of evaluable patients, when whole antigen vaccines are used. This was recently documented by Gulley et al (2002) in a trial with a recombinant vaccinia vector encoding PSA, where only five of the 42 enrolled patients could be immunologically tested.…”

Section: Discussionmentioning

confidence: 99%

A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer

et al. 2004

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Prostate-specific antigen (PSA) is a serine protease secreted at low levels by normal luminal epithelial cells of the prostate and in significantly higher levels by prostate cancer cells. Therefore, PSA is a potential target for various immunotherapeutical approaches against prostate cancer. DNA vaccination has been investigated as immunotherapy for infectious diseases in patients and for specific treatment of cancer in certain animal models. In animal studies, we have demonstrated that vaccination with plasmid vector pVAX/ PSA results in PSA-specific cellular response and protection against tumour challenge. The purpose of the trial was to evaluate the safety, feasibility and biological efficacy of pVAX/PSA vaccine in the clinic. A phase I trial of pVAX/PSA, together with cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) (Molgramostim) and IL-2 (Aldesleukin) as vaccine adjuvants, was carried out in patients with hormone-refractory prostate cancer. To evaluate the biologically active dose, the vaccine was administered during five cycles in doses of 100, 300 and 900 mg, with three patients in each cohort. Eight patients were evaluable. A PSA-specific cellular immune response, measured by IFN-g production against recombinant PSA protein, and a rise in anti-PSA IgG were detected in two of three patients after vaccination in the highest dose cohort. A decrease in the slope of PSA was observed in the two patients exhibiting IFN-g production to PSA. No adverse effects (WHO grade 42) were observed in any dose cohort. We demonstrate that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2 to patients with prostate cancer, is safe and in doses of 900 mg the vaccine can induce cellular and humoral immune responses against PSA protein.

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“…In another study, two synthetic decamer (10-mer) peptides corresponding to residues 141-150 and 154-163 of PSA were able to elicit CTL responses in vitro from normal HLA-A2 þ volunteers. 139 We have recently used tetramers for three PSA-derived peptides to directly quantify PSA-specific CD8 þ T cells in peripheral blood of non-vaccinated patients with PC and compared with a control group without cancer. 89,140 An example of visualization of PSA-specific CD8 þ T cells using tetramer staining is shown in Figure 3.…”

Section: Prostate-associated Antigens Recognized By Cd8 þ T Lymphocytmentioning

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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In Vitro Generation of Human Cytotoxic T Lymphocytes Specific for Peptides Derived From Prostate-Specific Antigen

Abstract: Our studies form a rational basis for the use of PSA peptides or recombinant vectors encoding PSA in the development of anticancer vaccine immunotherapy protocols for patients with prostate cancer.

Cited by 229 publications

References 31 publications

Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer

Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer

A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer

Immunology and immunotherapy approaches for prostate cancer

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