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Peripheral Blood CD4+ T-Cell Response Before Postoperative Active Immunotherapy Correlates with Clinical Outcome in Metastatic Melanoma

From the Department of Surgery at Saint Louis University (ECH), St. Louis, Missouri, and the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute of Saint John’s Health Center (EF, SS, XY, DLM), Santa Monica, California.

ABSTRACT

Background: Canvaxin polyvalent specific active immunotherapeutic (CancerVax Corp., Carlsbad, CA) is a minimally toxic adjuvant after resection of regional metastatic melanoma. Because Canvaxin immunotherapeutic requires induction of an immune response, we hypothesized that survival would be directly correlated with cellular immune responses to Canvaxin cells prior to immunization.

Methods: We randomly selected 54 patients from a study of Canvaxin therapy after complete resection of American Joint Committee on Cancer (AJCC) stage III melanoma. Peripheral blood lymphocytes (PBLs) collected before immunotherapy were co-cultured with Canvaxin cells; cellular response was determined by flow cytometric measurement of the production of intracellular interleukin 4 (IL4) or interferon gamma (IFN) by CD4⁺ T-cells. Results were calculated as percent positive for double staining of CD4⁺ plus IL4⁺ or CD4⁺ plus IFN⁺.

Results: The mean (± SD) increase in cytokine-producing CD4⁺ T-cells after Canvaxin stimulation was 4.8 ± 2.3% for an IFN response and 5.1 ± 2.0% for an IL4 response. Both increases were significantly correlated with overall survival by univariate analysis (P = .0471 for IFN and 0.002 for IL4). There was no significant correlation between unstimulated IFN/IL4 responses and overall survival. Multivariate analysis showed that a CD4⁺ T-cell IL4 response before Canvaxin therapy was a significant independent prognostic variable.

Conclusions: In vitro cellular immune response to Canvaxin cells directly correlates with survival after subsequent initiation of immunotherapy for AJCC stage III melanoma. This finding will be evaluated in a multicenter phase III trial of Canvaxin plus bacille Calmette-Guerin (BCG) versus placebo plus BCG after resection of stage III melanoma.

Key Words: Endogenous immune response • Immunotherapy • Melanoma

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