Overview: Experiments are being conducted to test the hypothesis that induction of immune responses that specifically target cancer stem cell (CSC) populations can inhibit tumor growth more effectively than conventional vaccines that target all tumor cells. The invention is a new method of vaccinating against cancer, which involves specifically targeting cancer stem cells (CSC) as the vaccine target, unlike current cancer vaccines, which target all tumor cells, rather than specifically stem cells. Since recent research indicates that CSC are responsible for initiating and maintaining tumor growth, vaccines that specifically target these cells may generate much more effective antitumor immunity than conventional vaccines that target all tumor cells non-specifically.
The new CSC vaccine would consist of several potential iterations. In the first and least refined example, CSC would be purified by FACS from tumor cell digests, then mixed with vaccine adjuvants and administered as a series of immunizations. The assay endpoints would increase protection from tumor challenge, compared to vaccines prepared from tumor cells that don’t contain any CSC.
In a second iteration, CSC vaccines would be used to identify specific CSC antigens, and the CSC-specific antigens would then be used as the actual tumor vaccine. The CSC antigens would be identified using immune assays and serum or T cells from animals or humans that were vaccinated with the crude CSC vaccine. Candidate antigens would then be validated using animal tumor challenge and vaccination experiments. A critical question to also be addressed is whether each type of tumor expresses unique tumor CSC, or whether a CSC antigen from one tumor type could be used to protect against other tumor types.
Once the CSC-specific antigens are identified, they could be cloned and incorporated into vaccines, using either recombinant CSC antigens or viral vectored vaccines that express the CSC antigen. These would be the preferred vaccines because of ease of production and scalability. It may also be preferable to produce CSC vaccines that contain multiple CSC antigens for increased breadth of tumor coverage.
Approach: Tumor vaccines were prepared from 4T1 breast cancer cells using fixed tumor cells plus CLDC adjuvant. Mice were vaccinated with the following 5 groups of cells:
1. No vaccine control
2. Vaccine prepared in conventional fashion using unseparated tumor cells
3. Vaccine prepared using the CD34+ CSC population of tumor cells
4. Vaccine prepared using the CD127+ CSC population of tumor cells
5. Vaccine prepared using tumor cells depleted of CD34+ and CD127+ CSC
Protocol: Mice were vaccinated s.c. once 10 days prior to tumor challenge with 4T1 tumor cells, then boosted once 7 days after the tumor cells were injected. Tumor growth was monitored every 2-3 days. At the completion of the experiment, tumor tissues were collected and analyzed for numbers of CD34+ or CD127+ CSC in the tumor tissues.