Abstract
Tumor cell-based vaccines use tumor cells as a source of tumor-associated antigens. In our study, we aimed to develop and test a tumor vaccine composed of tumor cells killed by irradiation combined with in vivo interleukin-12 gene electrotransfer as an adjuvant. Vaccination was performed in the skin of B16-F10 malignant melanoma or CT26 colorectal carcinoma tumor-bearing mice, distant from the tumor site and combined with concurrent tumor irradiation. Vaccination was also performed before tumor inoculation in both tumor models and tumor outgrowth was followed. The antitumor efficacy of vaccination in combination with tumor irradiation or preventative vaccination varied between the tumor models. A synergistic effect between vaccination and irradiation was observed in the B16-F10, but not in the CT26 tumor model. In contrast, up to 56% of mice were protected from tumor outgrowth in the CT26 tumor model and none were protected in the B16-F10 tumor model. The results suggest a greater contribution of the therapeutic vaccination to tumor irradiation in a less immunogenic B16-F10 tumor model, in contrast to preventative vaccination, which has shown greater efficacy in a more immunogenic CT26 tumor model. Upon further optimization of the vaccination and irradiation regimen, our vaccine could present an alternative tumor cell-based vaccine.
Highlights
The induction of effective antitumor immunity begins with the presentation of tumor-associated antigens (TAA) to antigen-presenting cells, such as dendritic cells (DC), through which the immune system can mount a specific antitumor response [1]
An in vivo study was performed in the B16‐F10 tumor model to determine the efficacy of the vaccination, i.e., non-viable tumor cells (NTC) surrounded by IL-12 gene electrotransfer (GET), distant from the locally irradiated tumor (10 Gy)
Pilot vaccination, i.e., NTC surrounded by IL‐12 GET, distant from the locally irradiated tumor
Summary
The induction of effective antitumor immunity begins with the presentation of tumor-associated antigens (TAA) to antigen-presenting cells, such as dendritic cells (DC), through which the immune system can mount a specific antitumor response [1]. Various immunotherapy approaches aim at restoring antitumor immunity Two such approaches that take advantage of patients’ own TAA are modified whole tumor cell vaccines [3,4,5,6,7] and vaccines prepared from tumor cell lysates [3,8,9,10,11,12,13,14]. Whole tumor cell vaccines are composed of patient-derived tumor cells which are ex vivo genetically modified to secrete immunological adjuvants and inactivated by irradiation [1,3,4,5,6,7]. Examples of such vaccines include Provenge, an Vaccines 2020, 8, 111; doi:10.3390/vaccines8010111 www.mdpi.com/journal/vaccines
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