The FDA Guidance on Therapeutic Cancer Vaccines: The Need for Revision to Include Preventive Cancer Vaccines or for a New Guidance Dedicated to Them

Abstract

Cancer vaccines based on antigens derived from self molecules rather than pathogens, have been under basic and clinical investigations for many years. Up until very recently they had been tested primarily in the setting of metastatic disease with the goal to engage the immune system in slowing down disease progression. Many therapeutic vaccine trials, either investigator-initiated or led by pharmaceutical companies, have been completed and many are currently ongoing, following the FDA Guidance on therapeutic cancer vaccines published in 2011. In recent years the target of cancer vaccines is being shifted to early cancer and even premalignant disease with the goal of preventing cancer. While some issues addressed in the FDA Guidance on therapeutic vaccines apply to preventive vaccines, many do not. Here we discuss a set of recommendations for revising the current Guidance to also cover preventive vaccines, or to include in a new Guidance dedicated specifically to vaccines for cancer prevention.

The importance of correctly timing cancer immunotherapy

“…This allows the vaccine to induce a protective immune response against the tumor antigens expressed by the type of cancer for which they are at risk [44]. Awareness of the regulatory authorities for this approach is very important to successfully combat cancer [45].…”

A Review on Nano-Based Drug Delivery System for Cancer Chemoimmunotherapy

“…With the deep understanding of tumor immunology and the success of Sipuleucel-T, several types of cancer vaccines and other diverse vaccines have now been evaluated in phase II and phase III clinical trials [39,40], such as granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-modified autologous tumor vaccine (CG8123), peptide-based glycoprotein 100 (Gp100), TGF-β2 antisense/GM-CSF gene-modified autologous tumor cell vaccine (TAG) and New York esophageal carcinoma antigen 1 Plasmid DNA (pPJV7611) [41][42][43]. Cancer vaccines often combined with adjuvants to produce powerful immune responses [44].…”

Recognizing and managing on toxicities in cancer immunotherapy

“…32 Most importantly, many cancer vaccine trials use the “3 + 3 design,” which may not be the most suitable approach to gathering dose-toxicity information from early phase trials, so that AEs are not able to be comprehensively and accurately assessed. 33…”

“…32 Most importantly, many cancer vaccine trials use the "3 + 3 design," which may not be the most suitable approach to gathering dose-toxicity information from early phase trials, so that AEs are not able to be comprehensively and accurately assessed. 33 Currently approved sipuleucel-T, a vaccine prepared by a 250-mL suspension containing a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF (prostate acid phosphatase-granulocyte-macrophage colony-stimulating factor), has mild toxicity, such as transient chills, fatigue, and fever within the first 24 h after the injection. The most common AEs, reported in patients treated by sipuleucel-T at a rate ≥15%, are chills, fatigue, fever, back pain, nausea, joint ache, and headache.…”