Various ways to improve whole cancer cell vaccines

Abstract

Immunotherapy based on whole cancer cell vaccines is regarded as a promising avenue for cancer treatment. However, limited efficacy in the first human clinical trials calls for more optimized whole cancer cell vaccines and better patient selection. It is suggested that whole cancer cell vaccines consist preferably of immunogenically killed autologous cancer stem cells associated with dendritic cells. Adjuvants should stimulate both immune effector cells and memory cells, which could be achieved through their correct dosage and timing of administration. There are indications that whole cancer cell vaccination is less effective in patients who are immunocompromised, who have specific genetic defects in their immune or cancer cells, as well as in patients in an advanced cancer stage. However, such patients form the bulk of enrolled patients in clinical trials, prohibiting an objective evaluation of the true potential of whole cancer cell immunotherapy. Each key point will be discussed.

Keywords::

• adjuvants
• immune memory
• immunogenic cell death
• whole cancer cell vaccines

Financial & competing interests disclosure

This work was supported by FWO grant G.0235.11N. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The major advantage of whole cancer cell vaccines is the induction of an active anticancer immune response leading to anticancer immune memory, which could lower cancer recurrence rates.

• Whole cancer cell vaccines can provide unique patient-specific antigens, enhancing the specificity of the anticancer treatment.

• The ideal whole cancer cell vaccine consists of immunogenically killed autologous cancer stem cells fused to autologous dendritic cells expressing an allogeneic molecule.

• Cancer cell characteristics, adjuvant type and the patient status should be considered when generating a whole cancer cell vaccine.

• Mice doses of antigen used in humans are likely ineffective at raising T-cell responses and should not be extrapolated.

• Whole cancer cell vaccines should be administered distant to the tumor, since tumor draining lymph nodes are likely immunosuppressive. The immunosuppressive features of the tumor should ideally be neutralized when applying active anticancer immunization.

• Evaluation of the true potential of whole cancer cell vaccine trials is often prohibited by an inappropriate patient selection.