Comparison of Dendritic Cell-Mediated Immune Responses among Canine Malignant Cells

Abstract

ABSTRACT. Dendritic cell (DC) vaccination is one of the most attractive immunotherapies for malignancies in dogs. To examine the differences in DC-mediated immune responses from different types of malignancies in dogs, we vaccinated dogs using autologous DCs pulsed with keyhole limpet hemocyanin (KLH) and cell lysate prepared from squamous cell carcinoma SCC2/88 (SCC-KLH-DC), histiocytic sarcoma CHS-5 (CHS-KLH-DC), or B cell leukemia GL-1 (GL-KLH-DC) in vitro. In vivo inductions of immune responses against these tumor cells were compared by the delayed-type hypersensitivity (DTH) skin test. The DTH response against SCC2/88 cells were observed in dogs vaccinated with autologous SCC-KLH-DC, while the response was undetectable against CHS-5 and GL-1 cells in dogs vaccinated with autologous CHS-KLH-DC and GL-KLH-DC. Skin biopsies taken from DTH challenge sites were then examined for immunohistochemistry, and recruitment of CD8 and CD4 T cells was detected at the site where SCC2/88 cells were inoculated in dogs vaccinated with SCC-KLH-DC. By contrast, neither CD8 nor CD4 T cell infiltration was found at the DTH challenge site in the dogs vaccinated with CHS-KLH-DC or GL-KLH-DC. These findings may reflect that the efficacy of immune induction by DC vaccination varies among tumor types and that immune responses could be inducible in squamous cell carcinoma. Our results encouraged further investigation of therapeutic vaccination for dogs with advanced squamous cell carcinoma in clinical trials. KEY WORDS: canine, delayed-type hypersensitivity, dendritic cell, malignancies, vaccination.J. Vet. Med. Sci. 69(9): 925-930, 2007 Dendritic cells (DCs) are the most potent antigen-presenting cells for initiating cellular immune responses through the activation of naïve T lymphocytes [3,20], making them the most attractive immunoregulatory cells for tumor immunotherapy. Recently, many clinical trials have been conducted on human patients with various types of tumors to evaluate the feasibility of immunization with DC vaccination, in which autologous DCs are loaded with defined tumor antigen such as synthetic peptide [19] and nucleotideencoding tumor antigen [10] or whole antigenic preparations such as tumor cell lysate [1]. These DC vaccinations have been proven to be effective for the induction of antitumor immunities and clinical responses in patients with several types of malignancies such as lymphoma [13,22], renal and prostate carcinoma [5,12], and especially melanoma [4,11]; however, the effectiveness of DC vaccination varies among tumor types. For example, some types of malignancies such as gastrointestinal malignancies, including colorectal, gastric, and hepatocellular carcinoma, are still not sufficient to show anti-tumor therapeutic effect [6,17]; nevertheless, the protocol of DC vaccination, including preparation of DC, loading antigen(s) to DC, and route of DC administration, are not yet well standardized to compare with other trials in different types of tumor.We have previously reported the in vivo induction of i...

Reading between the lines: molecular characterization of five widely used canine lymphoid tumour cell lines

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Immunotherapy for canine cancer – Is it time to go back to the future?

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Immunotherapy in Veterinary Oncology

“…A variety of approaches have been taken to date to focus the immune system on the aforementioned targets, including (1) whole-cell, tumor cell lysate, and/or subunit vaccines (autologous, or made from a patient's own tumor tissue; allogeneic, or made from individuals within a species bearing the same type of cancer; or whole-cell vaccines from g-irradiated tumor cell lines with or without immunostimulatory cytokines), 56,64-74 (2) DNA vaccines that immunize with syngeneic and/or xenogeneic (different species from recipient) plasmid DNA designed to elicit antigen-specific humoral and cellular immunity 75-77 (discussed later), (3) viral vector-based methodologies designed to deliver genes encoding TAAs and/or immunostimulatory cytokines, 78-82 (4) DC or CD40-activated B-cell vaccines (which are commonly loaded or transfected with TAAs, DNA or RNA from TAAs, or tumor lysates), [83][84][85][86][87][88][89][90] (5) adoptive cell transfer (the "transfer" of specific populations of immune effector cells to generate a more powerful and focused antitumor immune response), and (6) antibody approaches, such as monoclonal antibodies, 91 anti-idiotype antibodies (an idiotype is an immunoglobulin sequence unique to each B lymphocyte, and therefore antibodies directed against these idiotypes are referred to as anti-idiotype), or conjugated antibodies. The ideal cancer immunotherapy agent would be able to discriminate between cancer and normal cells (ie specificity), be potent enough to kill small or large numbers of tumor cells (ie sensitivity), and, lastly, be able to prevent recurrence of the tumor (ie durability).…”