Vaccinia As A Cancer Vaccine

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The experience with vaccinia in the eradication of smallpox led to research into its use as an antitumor vaccine. Vaccinia was engineered to express tumor antigens and serve as a cancer vaccine. The size of the potential transgene that can be put into the vaccinia vector allows for flexibility in engineering, such that immune enhancing genes and antigenetic genes can be recombined into the genome. The immunostimulatory effects and efficient transcriptional machinery of the virus were utilized to create various cancer vaccine vectors (Table 2).

Recently, a phase I clinical trial of vaccinia expressing prostate specific antigen (PSA) in prostate cancer patients was published. In this trial the Wyeth strain virus was delivered intradermally every 4 wk for three doses without producing significant systemic toxicities. A cutaneous reaction, consistent with viral replication was seen in all patients treated with the virus at a dose of 2.65 x 107 pfu. Several patients developed T-cell immune responses to PSA associated with prolonged periods before disease progression (55). Another phase II clinical trial by the NCI examines the potential of three strains of recombinant vaccinia virus expressing either PSA, B7.1, or of the fowlpox virus expressing PSA. Vaccinia expressing the tumor antigen carcino embryonic antigen (CEA) has been studied clinically as a priming vaccine followed by a boost with avipox expressing CEA. This regimen consisted of 1 x 107 pfu Wyeth strain vaccinia

Table 2 Recent Clinical Trials

First author



Mastrangelo (58)


Regression of injected lesions.

Marshall (56)


No clinical response.

Mukherjee (68)


No clinical response.

Eder (55)


Stabilization of PSA levels.

Sanda (69)


Stabilization of PSA levels.

Conry (70)


No clinical response.

Tsang (71)


No clinical response.

Adams (67)


Response in cervical cancer.

Rochlitz (60)


Response in metastatic disease.

Greiner (57)



injected intradermally. Although specific T-cell immune responses were generated and the regimen was well tolerated, there were no positive clinical responses noted (56). Rochlitz et al. published their phase I trial of a modifed vaccinia (MVA strain) expressing human MUC1 for antigen specific immunotherapy in patients with advanced MUC 1 positive cancers (60). They found that patients tolerated repeated doses of the virus with minimal side effects and 1 of the 13 patients with advanced cancer showed a marked decrease in the size of his metastasis that lasted 14 mo. Greiner et al. developed a vaccinia expressing a triad of costimulatory molecules including B7.1, intercellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 combined with CEA to produce a vaccine against CEA expressing cancers. This virus, known as rV-CEA TRICOM or a recombinant vaccinia vector that carries a triad of costimulatory molecules, has been encouraging in preclinical studies and is now the focus of clinical trials (57).

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