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Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: An immunologic survival model

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Abstract

Background: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed-type hypersensitivity (DTH) responses that we previously correlated with survival. We hypothesized that early DTH responses to MCV and early humoral responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall survival. We tested this hypothesis by monitoring immunologic profiles in 59 patients with melanoma who were receiving MCV after surgical resection of regional lymph node or soft-tissue metastases.

Methods: Blood was drawn before vaccine administration, biweekly for 6 weeks, and then monthly. DTH to MCV was recorded at 0, 2, 4, and 8 weeks of MCV therapy. Mean antibody titers during the first 6-week interval were calculated. Changes in DTH were calculated as the difference between peak and prevaccine values (ΔDTH).

Results: At a median follow-up of 75.6 months (range 5–138), univariate analysis assigned prognostic significance to gender (p=0.046), lymph node involvement (p=0.024), ΔDTH (p=0.044), mean anti-90-kDa MAA IgG (p=0.0009), and mean anti-90-kDa MAA IgM (p=0.0014). In multifactorial analysis, only the three immunologic variables significantly impacted survival (p=0.046, 0.0005, and 0.0053, respectively). A mathematical model based on ΔDTH and mean anti-90-kDa MAA IgG and IgM titers closely approximated the observed individual and overall survival rates.

Conclusions: The correlation between overall survival and initial humoral/cellular immune responses to MCV immunotherapy may be useful in selecting patients most likely to benefit from prolonged adjuvant immunotherapy.

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Authors and Affiliations

  1. From the Roy E. Coats Research Laboratories, John Wayne Cancer Institute at Saint John's Hospital and Health Center, Santa Monica, California, USA

    Ralph C. Jones LCDR MC USN, Mark Kelley MD, Rishab K. Gupta PhD, J. Anne Nizze PA-C, Reynold Yee BS, Zacarias Leopoldo DDM, Karen Qi MS, Stacey Stern MS &  Donald L. Morton MD

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  1. Ralph C. Jones LCDR MC USN
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  2. Mark Kelley MD
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  3. Rishab K. Gupta PhD
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  4. J. Anne Nizze PA-C
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  5. Reynold Yee BS
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  6. Zacarias Leopoldo DDM
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  7. Karen Qi MS
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  9. Donald L. Morton MD
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The views expressed herein are those of the authors and do not necessarily reflect the views of the US Army, US Navy, Uniformed Services University of the Health Sciences, or the Department of Defense.

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Jones, R.C., Kelley, M., Gupta, R.K. et al. Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: An immunologic survival model. Annals of Surgical Oncology 3, 437–445 (1996). https://doi.org/10.1007/BF02305761

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  • DOI: https://doi.org/10.1007/BF02305761

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