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Humoral Immune Response to a Therapeutic Polyvalent Cancer Vaccine After Complete Resection of Thick Primary Melanoma and Sentinel Lymphadenectomy

Mathew H. Chung, Rishab K. Gupta, Eddy Hsueh, Richard Essner, Wei Ye, Reynold Yee, Donald L. Morton

From the Sonya Valley Ghidossi Vaccine Laboratory of the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA.

Address reprint requests to Donald L. Morton, MD, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404; email: mortond{at}jwci.org.

Purpose: A therapeutic polyvalent cancer vaccine (Canvaxin vaccine; CancerVax Corp, Carlsbad, CA) induces antibodies to a glycoprotein tumor-associated antigen (TA90). However, endogenous immune responses to TA90 have also been reported. This study examined anti-TA90 antibody responses with respect to the survival of patients who received adjuvant vaccine immunotherapy after resection of thick ( 4 mm) primary cutaneous melanoma.

Patients and Methods: Serum specimens were obtained from 54 patients immediately before and then 1, 2, 4, and 6 months after wide local excision of thick primary cutaneous melanoma and sentinel lymphadenectomy. All patients were offered adjuvant therapies with the vaccine, high-dose interferon, or other agents. An enzyme-linked immunosorbent assay was used to determine serial serum titers of immunoglobulin G (IgG) and IgM antibodies against TA90. These titers were correlated with clinical course.

Results: Forty-three patients chose vaccine therapy, and 11 patients chose postoperative observation. Preoperative anti-TA90 IgG and IgM titers were similar for vaccine and observation groups (P = .184). At a median follow-up of 26 months, univariate analysis of Cox regression showed that disease-free survival and overall survival of vaccine patients were significantly correlated with maximal IgM response (P = .0006 and .006, respectively) but not with maximal IgG response (P = .73 and .95, respectively). Neither response predicted survival in the observation group.

Conclusion: Postoperative vaccine therapy may enhance IgG and IgM immune responses to TA90 after surgical resection, but only the IgM response is correlated with improved survival. These findings may become useful to guide selection of patients for postoperative adjuvant therapy of high-risk melanoma.

Supported in part by grant nos. CA12582 and CA29605 from the National Cancer Institute, Bethesda, MD, and by funding from the Wayne and Gladys Valley Foundation, Oakland, CA, and the Harold McAlister Charitable Foundation, Los Angeles, CA.

Presented at the Thirty-Seventh Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 15–19, 2001.

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