Abstract
Active immunotherapy against cancer is based on immune system stimulation, triggering efficient and long-lasting antigen-specific immune responses. Immunization strategies using whole dead cells from tumor tissue, containing specific antigens inside, have become a promising approach, providing efficient lymphocyte activation through dendritic cells (DCs). In this work, we generate whole dead tumor cells from CT26, E.G7, and EL4 live tumor cells as antigen sources, which termed immunogenic cell bodies (ICBs), generated by a simple and cost-efficient starvation-protocol, in order to determine whether are capable of inducing a transversal anticancer response regardless of the tumor type, in a similar way to what we describe previously with B16 melanoma. We evaluated the anticancer effects of immunization with doses of ICBs in syngeneic murine tumor models. Our results showed that mice's immunization with ICBs-E.G7 and ICBs-CT26 generate 18% and 25% of tumor-free animals, respectively. On the other hand, all carrying tumor-animals and immunized with ICBs, including ICBs-EL4, showed a significant delay in their growth compared to not immunized animals. These effects relate to DCs maturation, cytokine production, increase in CD4+T-bet+ and CD4+ROR-γt+ population, and decrease of T regulatory lymphocytes in the spleen. Altogether, our data suggest that whole dead tumor cell-based cancer immunotherapy generated by a simple starvation protocol is a promising way to develop complementary, innovative, and affordable antitumor therapies in a broad spectrum of tumors.
Highlights
Active immunotherapy against cancer aims to trigger efficient and long-lasting, antigen-specific immune responses
We generated immunogenic whole dead tumor cells as antigens sources termed immunogenic cell bodies (ICBs), using a simple and cost-efficient starvation method described previously by us [14], compared to the others previously described, which can be reproduced in a wide spectrum of research laboratories [15, 16]. These ICBs were generated from different tumor cell lines, lymphoma EL4/E.G7 and colon cancer CT26. This was done in order to determine whether our ICBs are capable of inducing a broad-spectrum anticancer response, regardless of the tumor type, in a similar way to what we describe with B16 melanoma [13]
In order to determine whether this antitumor effect of our ICBs generated are reproducible in other types of cancer cells, we evaluated the effect on lymphoma model EL4 and EG-7 (EL4 expressing OVA)
Summary
Active immunotherapy against cancer aims to trigger efficient and long-lasting, antigen-specific immune responses. Cell death is a process that varies according to the cytotoxic stimulus; this influences immunogenic/anticancer potential of the cellular compounds generated during cell death. This has led researchers to coin the term immunogenic cell death (ICD) to refer to the type of death that best induces immunogenic responses [4, 5]. Immunogenic cell death depends largely on the death-initiating stimulus that could cause the exposure of immunogenic factors on the cell surface or the release of immunogenic signals into the extracellular space [6] This can result from multiple cytotoxic stimuli and protocols, some of which have shown efficacy in clinical and preclinical experiments. A variety of chemotherapeutic drugs, such as anthracyclines and oxaliplatin [7], and lethal doses of ultraviolet (UV) rays and gamma irradiation, to generating apoptotic tumor cells [8] can induce immunogenic tumor cells death
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