Cancer Vaccine Platforms
Some approved cancer therapies employ immunological mediates, but are not considered vaccines. Interleukin-2 (IL-2, Proleukin
for treating melanoma and renal cell carcinoma),2 alpha-interferon (IFN-α, Intron A to treat various cancers)3 and monoclonal antibodies (e.g., Trastuzumib, which binds the HER2 epidermal growth factor receptor on breast cancer)4 are familiar cancer therapy agents. For this review, however, the focus is on cancer vaccines, which as defined above, introduce
TAAs to the patient to elicit an effective tumor immune response. Two categories of cancer vaccines that differ in their technical
complexity will be discussed.
Tumor Antigen–Based Vaccines
Tumor antigen–based vaccines can be viewed as traditional vaccines that are approved for prevention of infectious diseases.
The vaccine consists of an antigen formulated with or without an adjuvant or immunostimulator to enhance immunogenicity. Recombinant
proteins, peptides, soluble tumor lysates, and killed tumor cells are used as TAAs in these cancer vaccines. The simplest
of these vaccines consists of full length protein or peptide TAAs in a suitable pharmaceutical vehicle for parenteral delivery.
Examples of protein- or peptide-based cancer vaccines in clinical development include:
- IDM Pharma's EP-2101 vaccine, which consists of nine synthetic peptides based on epitopes from four TAAs for treatment of
non-small cell lung cancer. Promising interim results from a 68-patient Phase 2 clinical trial were recently reported.5
- PROSTVAC-VF, the Therion Biologies vaccine for treatment of prostate cancer.6 The vaccine consists of two genetically engineered viruses (vaccinia and fowlpox given as prime and boost vaccinations,
respectively) that express PSA and three co-stimulatory molecules, B7.1, ICAM-1, and LFA-3 (TRICOM).
- The Favrille vaccine (Favld, for treatment of B-cell non-Hodgkin's lymphoma) uses genetic engineering to produce a recombinant
protein of the patient's B-cell idiotype, the TAAs specific to that cancer.7 The idiotype antigen is conjugated with keyhole limpet hemocyanin (KLH), an immunostimulatory molecule that is then formulated
with granulocyte macrophage colony stimulating factor (GM-CSF), which is a potent stimulator of APCs.
Autologous and allogeneic (patient unrelated) tumor cells can be used as cancer vaccines. For these vaccines, either a crude,
soluble cell lysate or whole, killed tumor cells are formulated for injection. Tumor-cell vaccines are often a mixture of
TAAs and nonantigenic cellular components. An example of this type of vaccine is Cell Genesys's GVAX for prostate cancer.
This vaccine comprises two prostate cancer cell lines, LNCaP and PC-3, which, in addition to expressing several TAAs, were
transduced to express GM-CSF. In a Phase 1–2 clinical trial, 16/21 (76%) hormone-naive prostate cancer patients had a significant
decrease in PSA velocity and increased TAA antibody titers at 12 weeks following eight weekly intradermal injections of the
vaccine.8 Phase 3 clinical trials with this vaccine are under way. The GVAX technology for autologous and allogeneic tumor cell vaccines
is being applied to a variety of cancers.9
Cell–Based Vaccines
Table 1. Summary of dendritic-cell vaccine platforms
|
Cell-based vaccines use ex vivo–prepared TAA-loaded APCs as the vaccine.10 Table 1 provides an overview of the array of technology platforms. Briefly, the patient's APCs are isolated from peripheral
blood cells and placed in cell culture for loading with TAAs. For many of these vaccines, the precursor monocytes or CD34+
cells are cultured with cytokines to obtain dendritic cells (DC), which are very potent APCs.12 Examples of these types of vaccines include:
|
