When a macrophage engulfs and breaks down a tumor cell harboring a PSA molecule, other tumor-specific protein fragments are released. These tumor-specific fragments then serve as antigens and elicit an immune response, generating even more antitumor antibodies and T-cell interactions. Thus the tumor regresses. Importantly, this type of vaccine can be mass produced.
Vaccines With Chemotherapy
Another approach to the design of a tumor-specific vaccine is based on tumor-associated peptides (TUMAPs). These TUMAPs are highly overexpressed in tumors relative to a number of normal, healthy tissues. Nine highly immunogenic TUMAPs from 80 specimens of the same tumor type, identified by mass spectrometry, gene expression profiling, literature-based functional assessment, bioinformatics, and human T-cell assays, are used to prepare IMA901, a multipeptide vaccine against the specific tumor, renal cell carcinoma. The pool of selected peptides, composed of 9 to 16 amino acids, is then administered to patients following a dose of the immunomodulator GM-CSF for a total of as many as 17 injections. Low-dose cyclophosphamide administered prior to the first vaccination downregulates regulator T cells, enhancing immune response and resulting in prolonged survival. 13 This type of vaccine can also be mass produced.
Conclusions
The vaccines that are currently in use or in clinical trials are being used in patients with advanced disease. As such, they are therapeutic rather than prophylactic. It is inevitable that more vaccines will earn FDA approval. Eventually, they will be used in earlier-stage disease. It is conceivable that some can be used prophylactically when a malignancy first becomes detectable, especially as more sensitive detection methods are developed. Vaccine delivery systems are likely to change as researchers investigate and adopt matrix materials that increase efficacy.
Cancer vaccines hold the potential for greater selectivity in treatment of malignancies. These vaccines may enable us to use cytotoxic chemotherapy agents less often or perhaps more effectively when used in conjunction with vaccines. Vaccines that can be mass produced could conceivably decrease the financial burden of cancer treatment as well as the human cost of malignant diseases and their therapy and care requirements.
Solid-tumor and hematologic malignancy vaccines are coming into wider use as the science is better understood and more methods of generating immune responses are explored. A personalized cancer vaccine, sipuleucel-T, is FDA approved for clinical use against mCRPC.9 A poxvirus-based vaccine, PROSTVAC, also against mCRPC, is in phase 3 clinical trials. 10,11 The multipeptide renal cell carcinoma vaccine IMA901 is also in phase 3 clinical trials. 13 A personalized vaccine against glioblastoma multiforme CSCs has extended progression-free survival in its initial pretrial study. 8,14 Additional glioblastoma, melanoma, and other vaccines are in clinical trials and under development.
Author disclosures
The author reports no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the author and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
