A heat-shocked melanoma cell lysate vaccine enhances tumor infiltration by prototypic effector T cells inhibiting tumor growth.

Journal for Immunotherapy of Cancer
María Alejandra GleisnerFlavio Salazar-Onfray

Abstract

Immune checkpoint blocker (ICB) therapy has shown survival benefits for some patients with cancer. Nevertheless, many individuals remain refractory or acquire resistance to treatment, motivating the exploration of complementary immunotherapies. Accordingly, cancer vaccines offer an attractive alternative. Optimal delivery of multiple tumor-associated antigens combined with potent adjuvants seems to be crucial for vaccine effectiveness. Here, a prototype for a generic melanoma vaccine, named TRIMELVax, was tested using B16F10 mouse melanoma model. This vaccine is made of heat shock-treated tumor cell lysates combined with the Concholepas concholepas hemocyanin as adjuvant. While B16F10 lysate provides appropriate melanoma-associated antigens, both a generic human melanoma cell lysate and hemocyanin adjuvant contributes with danger signals promoting conventional dendritic type 1 cells (cDC1), activation, phagocytosis and effective antigen cross-presentation. TRIMELVax inhibited tumor growth and increased mice survival, inducing cellular and humoral immune responses. Furthermore, this vaccine generated an increased frequency of intratumor cDC1s but not conventional type 2 dendritic cells (cDC2s). Augmented infiltration of CD3+, CD...Continue Reading

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Methods Mentioned

BETA
flow cytometry
FACS
ELISA
flow
genetic modifications

Software Mentioned

TAPCell
FlowJo10
GraphPad Prism

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