The biological effects of syngeneic and allogeneic cytokine-expressing prophylactic whole cell vaccines and the influence of irradiation in a murine melanoma model

Abstract

Allogeneic whole tumour cell vaccines are inherently practical compared with autologous vaccines. Cell lines are derived from allogeneic tumour, grown in bulk and then administered as a vaccine to the patient, following irradiation, which not only prevents any replication but also enhances antigen presentation. Protection is believed to occur through the presentation of antigens shared between the syngeneic and allogeneic tumours. Although cytokine-transfected tumour whole cell vaccines have been used clinically, little data is available comparing the effects of immunomodulatory cytokine-transfection directly on the same cells when used as both an allogeneic and autologous vaccine. To address this, weakly immunogenic B16-F10 (H-2b) murine melanoma was transfected to secrete either GM-CSF, IL-4 or IL-7. Prophylactic vaccination of both syngeneic C57/BL6 (H-2b) (B6) and allogeneic C3H/Hej (H-2k) (C3H) mice showed the effects of transfected cytokine varied between models. Both GM-CSF and IL-7 significantly (P<0.05) increased the levels of protection within syngeneic B6 mice, but had a diminished effect (P>0.05) within C3H allogeneic mice. Allogeneic B16-F10 cells and syngeneic K1735 cells generated CTL against K1735 suggesting cross-reactive immunity. Using cells labeled with fluorescent dye we demonstrate that irradiated vaccines, of either syngeneic or allogeneic origin, appear to generate potent immune responses and fragments of either vaccine remain at the injection site for up to 9 days. This study shows that protection can be enhanced in vivo by using transfected cytokine, but suggests that irradiated whole cell vaccines, of either tissue-type, are rapidly processed. This leads to the conclusion that the cytokine effects are transient and thus transfection with cytokine may be of limited long-term use in situ.

Ultra scale‐down stress analysis of the bioprocessing of whole human cells as a basis for cancer vaccines

“…5) indicate that the surface marker density may reduce from 10% for most markers up to 30% for CD9 in the OnyCap23 cell line. The retention of antigen load of the correct conformation is generally accepted as being a good surrogate of vaccine activity for more established vaccines and evidence suggests that in vivo cells are lysed and processed by the immune system within 9 days post‐injection (Labarthe et al, 2006). However, for novel, cell‐based therapeutic vaccines antigen density or confirmation alone may not be a sufficient surrogate, as the intended biological effect in vivo is often not clear, and cell membrane integrity may also be important (European Medicines Agency, 2007).…”

Evaluation of a Novel Tumor Vaccine in Dogs with Hemangiosarcoma

“…This approach holds promise because many tumors of the same histiotype may share common antigens, so that vaccination against one tumor may elicit cross-reactive immune responses against other tumors of the same type. 34,40,41 An allogeneic tumor lysate vaccine for melanoma has been evaluated in a number of clinical trials in humans and has shown clinical benefit in an adjuvant setting. 42,43 Vaccines prepared with tumor cell lysates are particularly promising because of the ease of preparation, storage, and shipping of the vaccine.…”

Overview of Tumor Cell–Based Vaccines

“…Studies in animal models indicate that vaccination with an allogeneic tumor of the same type (i.e., melanoma treated with a melanoma cell line) can induce rejection of a tumor while treatment with cell lines of a different cancer background does not [20,21] and, moreover, they can subsequently induce strong responses to autologous cell lines. However, not all allogeneic melanoma cell lines were protective in a melanoma model indicating a level of heterogeneity within cancer lines of the same type [20].…”