Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma

Hersey, Peter; Edwards, Anne; Coates, Alan S.; Shaw, Helen M.; McCarthy, William H.; Milton, G. W.

doi:10.1007/bf00199156

Cited by 63 publications

(35 citation statements)

References 40 publications

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“…These include vaccination with autologous, hapten-modified tumor cells in conjunction with bacillus Calmette-Guérin and cyclophosphamide (17); immunization with allogeneic melanoma cells in a variety of forms, including intact cells or shed antigens with bacillus Calmette-Guérin, viral-modified cell lysates, and cell lysates admixed with complex adjuvants (18)(19)(20)(21)(22); and vaccination with defined melanoma antigens such as the ganglioside GM2 or peptides derived from the MAGE and melanocyte differentiation protein families (23)(24)(25)(26). Whereas differences in patient population and immunologic evaluation render it difficult to compare the results of these vaccination schemes with the findings reported here, several similarities with the studies using hapten-modified tumor cell vaccinations nonetheless are evident.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma

Soiffer

Lynch

Mihm

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

510

277

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We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocytemacrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte-macrophage colonystimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

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Section: Discussionmentioning

confidence: 99%

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma

Soiffer

Lynch

Mihm

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

510

277

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“…According to data from Hersey [3] and Wallack's group [14], the survival time of melanoma patients could be significantly prolonged by i.d. injection of VV-melanoma oncolysates with minimal side effects.…”

Section: Discussionmentioning

confidence: 99%

Establishment of tumor‐specific immunotherapy model utilizing vaccinia virus‐reactive helper T cell activity

et al. 1988

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It was previously demonstrated that preimmunization of mice with live vaccinia virus (VV) and subsequent immunization with VV-infected (modified), syngeneic tumor cells resulted in enhanced induction of tumor-specific immunity through a cellular collaboration between VV-reactive helper T (VV-Th) cells and tumor-specific effector cell precursors. On the basis of this augmenting system, a tumor-specific immunotherapy model was established in which a growing tumor regressed. C3H/HeN mice were pretreated with cyclophosphamide to eliminate nonspecific suppressor T cell activity and subsequently inoculated (primed) s.c. with live VV, leading to augmented induction of VV-Th cell activities. Four weeks later, the mice were inoculated i.d. with syngeneic X5563 myeloma cells. Six days after the tumor cell inoculation, live VV was injected into the tumor mass three times at 2-day intervals. Seven of ten mice which had received VV priming and subsequent VV injection into the tumor mass exhibited complete tumor regression. On the contrary, mice which had received mere intratumoral VV injection in the absence of VV priming failed to exhibit appreciable tumor regression. Mice whose tumor had completely regressed (regressor mice) by the above VV immunotherapy were shown to have acquired systemic anti-tumor immunity, which was confirmed by a challenge with syngeneic tumor cells after the tumor regression. In vitro analysis of these immune mice revealed that potent tumor-specific cytotoxic T lymphocyte responses were preferentially induced, but with no detectable anti-tumor antibody responses. Such a potent tumor-specific immunity was not observed in mice which had received an intratumoral VV injection in the absence of VV priming. Thus the results clearly indicate that the tumor regression was accompanied by concurrent generation of a potent tumor-specific immunity, suggesting that the cellular collaboration between VV-Th cells and tumor-specific effector cell precursors is also functioning in this VV-immunotherapy protocol, likewise the immunoprophylactic model. Therefore, the present model provides an effective maneuver for tumor-specific immunotherapy and this system will be theoretically applicable to human cancer treatment.

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“…Examples of antigen modifications that have been attempted to augment the immunogenicity of melanoma antigens includes physical aggregation of the antigens, neuraminidase treatment [8], and infecting the melanoma cells with live nonpathogenic viruses [5,7,11]. Melanoma antigens have been coated unto liposomes or incorporated into vaccinia virus to enable their presentation in multimeric units.…”

Section: Potentiating Vaccine Immunogenicitymentioning

confidence: 99%

“…Most involve the use of whole tumor cells. The cells are either used intact [12,9], or after they have been broken up mechanically with detergents or other treatments, or lysed with non-pathogenic viruses such as vaccinia [5,11,7], Newcastle disease [5], or VSV [38]. The bulk of the material in such vaccines is derived from the cytoplasm, rather than from the surface of the cells, and is thus irrelevant to vaccine activity.…”

Section: Collection Of Tumor Antigens For Vaccine Productionmentioning

confidence: 99%

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Tumor vaccines

Bystryn

1990

Cancer Metast Rev

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Melanoma vaccines are an exciting and increasingly attractive immunotherapeutic approach for malignant melanoma. Vaccines can be used for patients with high risk primary melanoma and regional disease, stages in the progression of melanoma for which there is presently no treatment. They are unique in their potential to prevent cancer in high risk individuals. Multiple approaches are being followed to develop effective vaccines. It is too early to judge whether any of them effectively slow the progression of melanoma. However, it is clear that vaccines are safe to use, and that they can stimulate immune responses to melanoma in some patients. The specificity of these responses needs to be clarified, and multiple challenges remain to be overcome before effective vaccines to melanoma become available. We must first identify the antigens on melanoma that stimulate immune responses, define the immune effector mechanisms that are stimulated by vaccine immunization and identify those responsible for increasing resistance to tumor growth, devise appropriate ways of constructing vaccines that will induce such responses, and find adjuvants and/or immunodulators that will potentiate desirable immune responses.

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Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma

Cited by 63 publications

References 40 publications

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte–macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma

Establishment of tumor‐specific immunotherapy model utilizing vaccinia virus‐reactive helper T cell activity

Tumor vaccines

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