open access: Expert Reviews - Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm (ovarian/breast)

Expert Reviews - Expert Review of Vaccines - 11(3):275 - Full Text
  
Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm

Key issues

	• Heterologous prime—boost regimen with antigenically diverse recombinant poxviruses encoding for tumor-associated antigens and B7.1/ICAM-1/LFA3 cassette represents a most promising vaccination schedule inducing clinical and immunological responses.
	• PANVAC shows clinical efficacy in patients with metastatic breast and ovarian cancers.
	•  Patients with limited tumor burden and minimal prior chemotherapy had a benefit from PANVAC vaccination.
	• PANVAC was demonstrated to be immunologically active in some of the patients who developed clinical responses.
	• Overall survival, rather than progression-free survival, may be more relevant for addressing the effects of therapeutic cancer vaccines.
	• PANVAC, as also other cancer vaccines, elicits a dynamic process of immune responses, which may be exploited in subsequent therapies.
	• Vaccines used in the adjuvant setting (i.e., in patients with low tumor burden following conventional treatment) may be more efficacious than in patients with more advanced disease having increased tumor load.
	• Immunological end points as intermediate markers are needed for assessing clinical efficacy shortly after vaccination. Five-year view "The ultimate goal of therapeutic cancer vaccines should be to reduce the risk of recurrences in cancer patients with minimal residual disease or with no evidence of disease. In this case, therapeutic cancer vaccines, such as PANVAC, should be applied in the adjuvant setting after conventional therapies. However, therapeutic vaccination may also be applied in the metastatic setting, albeit in this case, it will likely need to be combined with chemotherapy. Considering the time of translation of vaccination-induced immune responses into clinical efficacy, median OS in the group of vaccinated patients may be affected at much later time points after treatment initiation compared to the group of patients receiving chemotherapy. Therefore, it becomes mandatory to plan clinical trials in such a way as to include start of assessments of clinical efficacy at later time points, which will also allow a better planning for interim analyses. OS as an end point for clinical vaccine trials poses a problem for making decisions about treatment efficacy after short-term assessment. Thus, there is a need for standardized immunological biomarkers as intermediate end points, which will be useful to determine clinical benefit shortly after immunotherapy. Such immunological end points will be essential to demonstrate the development of vaccine-induced immune responses and their clinical relevance. Novel immune-related response criteria are also essential for assessing clinical activity of cancer vaccines. Thus, developing optimized cancer vaccines and combining those with modalities aimed at improving their anticancer activity in well-designed clinical trials will open new avenues for the design of clinically effective cancer vaccine strategies. In this scenario, PANVAC may play a significant role in cancer immunotherapy for appropriately selected patients with cancer." Financial & competing interests disclosure   The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter discussed in the article. This includes employment, consultancies, stock ownership or options, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this article.