2015 Guidance on cancer immunotherapy development in early‐phase clinical studies

Abstract

The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of “cancer vaccines”, which are based on the idea of vaccination, “effector cell therapy”, classified as passive immunotherapy, and “inhibition of immunosuppression”, which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor‐infiltrating lymphocytes and tumor‐specific receptor gene‐modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors.

Characteristics of the specific humoral response in patients with advanced solid tumors after active immunotherapy with a VEGF vaccine, at different antigen doses and using two distinct adjuvants

“…This is in line with the fact that it is generally recognized that many cancer vaccines have few adverse reactions [24]. …”

“…Although these types of correlations are not applicable to phase I clinical trials, there is no doubt about the importance of studying in depth the humoral response in early evaluations of cancer vaccines in humans [24]. A special emphasis was done in this paper in the characterization of the vaccine-induced humoral response in terms of quantity, quality, kinetic, dynamic and composition.…”

Characterization of immune cell subtypes in three commonly used mouse strains reveals gender and strain-specific variations

“…The methodology of conducting immunophenotypic analysis of different cell populations can vary considerably from one study to another based on the endpoints and the goals of the study 24, 29, 31, 32 . For instance, different studies may report immune cell percentages in distinct ways based on normalization strategies and gating methods (e.g.…”

“…However, many such studies are designed to focus on the biology of only specific leukocyte subpopulations in response to treatments with experimental agents 7, 18–23 . Based on the experimental design of the immunological study, in vivo experiments are carried out in different mouse strains and immune profiles are evaluated at different steps following treatment regimen 24 . The variations in experimental variables such as mouse strain, animal physiology, age, gender, drug combinations, time-points, dose, treatment strategies, tumor sub-types and tumor inoculation methods can create infinite confounders that influence the immune parameters and need to be considered even for a study with a single agent 7, 9–15, 24–30 .…”

Cancer Vaccines in Ovarian Cancer: How Can We Improve?

“…Finally, another consideration is the vaccination schedule, in terms of dose, number of injections and time, to initiate and maintain the appropriate immune response. More studies are warranted to determine which of those elements (alone and in combination) would offer optimal clinical efficacy [ 23 ]. Here, we will summarize the results obtained to date with all types of vaccination strategies in ovarian cancer with the intent to provide a general overview allowing undertaking more rational decisions ( Table 1 ).…”