Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen

Sattva S. Neelapu, Sivasubramanian Baskar, Barry L. Gause, Carol B. Kobrin, Thelma M. Watson, Andrea Robin Frye, Robin Pennington, Linda Harvey, Elaine S. Jaffe, Richard J. Robb, Mircea C. Popescu, Larry W. Kwak

Research output: Contribution to journalArticle

Abstract

Purpose: The idiotype (Id) of the immunoglobulin on a given B-cell malignancy is a clonal marker that can serve as a tumor-specific antigen. We developed a novel vaccine formulation by incorporating Id protein with liposomal lymphokine that was more potent than a prototype, carrier-conjugated Id protein vaccine in preclinical studies. In the present study, we evaluated the safety and immunogenicity of this vaccine in follicular lymphoma patients. Experimental Design: Ten patients with advanced-stage follicular lymphoma were treated with five doses of this second generation vaccine after chemotherapy-induced clinical remission. All patients were evaluated for cellular and humoral immune responses. Results: Autologous tumor and Id-specific type I cytokine responses were induced by vaccination in 10 and 9 patients, respectively. Antitumor immune responses were mediated by both CD4+ and CD8+ T cells, were Iranian lymphocyte antigen class I and II associated, and persisted 18 months beyond the completion of vaccination. Specific anti-Id antibody responses were detected in four patients. After a median follow-up of 50 months, 6 of the 10 patients remain in continuous first complete remission. Conclusions: This first clinical report of a liposomal cancer vaccine demonstrates that liposomal delivery is safe, induces sustained tumor-specific CD4+ and CD8 + T-cell responses in lymphoma patients, and may serve as a model for vaccine development against other human cancers and infectious pathogens.

Original languageEnglish (US)
Pages (from-to)8309-8317
Number of pages9
JournalClinical Cancer Research
Volume10
Issue number24
DOIs
StatePublished - Dec 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Neelapu, S. S., Baskar, S., Gause, B. L., Kobrin, C. B., Watson, T. M., Frye, A. R., Pennington, R., Harvey, L., Jaffe, E. S., Robb, R. J., Popescu, M. C., & Kwak, L. W. (2004). Human autologous tumor-specific T-cell responses induced by liposomal delivery of a lymphoma antigen. Clinical Cancer Research, 10(24), 8309-8317. https://doi.org/10.1158/1078-0432.CCR-04-1071