Phase I Study in Advanced Cancer Patients of a Diversified Prime-and-Boost Vaccination Protocol Using Recombinant Vaccinia Virus and Recombinant Nonreplicating Avipox Virus to Elicit Anti–Carcinoembryonic Antigen Immune Responses

Marshall, John L.; Hoyer, Robert J.; Toomey, Mary Ann; Faraguna, Kristen; Chang, Ping; Richmond, Ellen; Pedicano, James E.; Gehan, Edmund A.; Peck, Ronald; Arlen, Philip M.; Tsang, Kwong Y.; Schlom, Jeffrey

doi:10.1200/jco.2000.18.23.3964

Cited by 311 publications

(137 citation statements)

References 20 publications

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“…Further increases in CEA-specific T-cell precursors were seen when local granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose interleukin (IL)-2 were given with subsequent vaccinations. 117 Direct transfer of cytokine genes to tumor cells has emerged as a third immunotherapeutic tool in oncolytic virotherapy to increase its antitumor efficacy. The rationale behind this approach is that expression of cytokine genes in tumor cells, delivered by oncotropic viruses, will stimulate inflammatory and immune responses against these cells, thereby enhancing the antitumor effects of oncolytic viruses.…”

Section: Enhancement Of Viral Intrinsic Antitumor Potencymentioning

confidence: 99%

Replication-selective oncolytic viruses in the treatment of cancer

2004

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In the search for novel strategies, oncolytic virotherapy has recently emerged as a viable approach to specifically kill tumor cells. Unlike conventional gene therapy, it uses replication competent viruses that are able to spread through tumor tissue by virtue of viral replication and concomitant cell lysis. Recent advances in molecular biology have allowed the design of several genetically modified viruses, such as adenovirus and herpes simplex virus that specifically replicate in, and kill tumor cells. On the other hand, viruses with intrinsic oncolytic capacity are also being evaluated for therapeutic purposes. In this review, an overview is given of the general mechanisms and genetic modifications by which these viruses achieve tumor cell-specific replication and antitumor efficacy. However, although generally the oncolytic efficacy of these approaches has been demonstrated in preclinical studies the therapeutic efficacy in clinical trails is still not optimal. Therefore, strategies are evaluated that could further enhance the oncolytic potential of conditionally replicating viruses. In this respect, the use of tumor-selective viruses in conjunction with other standard therapies seems most promising. However, still several hurdles regarding clinical limitations and safety issues should be overcome before this mode of therapy can become of clinical relevance.

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Section: Enhancement Of Viral Intrinsic Antitumor Potencymentioning

confidence: 99%

Replication-selective oncolytic viruses in the treatment of cancer

2004

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“…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.…”

mentioning

confidence: 99%

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

Gulley¹,

Arlen²,

Bastian³

et al. 2005

Clinical Cancer Research

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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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“…An ongoing clinical trial is using rV-PSA prime vaccination followed by multiple avipox-PSA boosts. In a phase I clinical trial, Marshall et al showed that rV-CEA followed by multiple avipox-CEA inoculations (VAAA strategy) in randomized patients was significantly more potent in inducing CEA-specific Tcell precursor frequency than the converse AAAV treatment [21]. In addition, this difference appeared to be clinically relevant, as there was a statistically significant increase in survival in the VAAA arm (P ¼ 0.0018).…”

Section: Discussionmentioning

confidence: 95%

Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV‐PSA) in patients with metastatic androgen‐independent prostate cancer

et al. 2002

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BACKGROUNDA Phase I trial of recombinant vaccinia prostate specific antigen (rV‐PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations.METHODSAll patients were entered on a dose‐escalation phase I study of recombinant vaccinia containing the gene for PSA (rV‐PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen‐independent prostate cancer patients. A secondary objective was to assess evidence of anti‐tumor activity by PSA measurements, radiologic findings, and immunologic methods.RESULTSThere was no significant treatment‐related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA‐specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA‐expressing tumor cells in vitro.CONCLUSIONGiven the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA‐based vaccines in prostate cancer. New PSA‐based vaccines and vaccine strategies are currently being evaluated. Prostate 53: 109–117, 2002. © 2002 Wiley‐Liss, Inc.

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Phase I Study in Advanced Cancer Patients of a Diversified Prime-and-Boost Vaccination Protocol Using Recombinant Vaccinia Virus and Recombinant Nonreplicating Avipox Virus to Elicit Anti–Carcinoembryonic Antigen Immune Responses

Cited by 311 publications

References 20 publications

Replication-selective oncolytic viruses in the treatment of cancer

Replication-selective oncolytic viruses in the treatment of cancer

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

Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV‐PSA) in patients with metastatic androgen‐independent prostate cancer

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