Everything that has been suggested, thus far, looks like good science to me. But I don't "get" AGEN. I think that the adjuvant concept is fine, but....
antigenics.com
For decades it has been known that animals can be ‘vaccinated’ against cancer. This is how it works: Tumor cells can be weakened, or attenuated, and injected like a vaccine into a mouse. Afterwards, if these same tumor cells, at full strength, are injected into the mouse, the mouse will reject the tumor cells and cancer will not develop. However, if a mouse has not been vaccinated in this manner, the tumor cells will ‘take’ and the mouse will develop cancer.
This is complete and total BS, and they know it. Yes, it works fine for *induced* cancers, cancers that are elicited with either a virus or a strong carcinogen.......
Int J Cancer. 1977 Nov 15;20(5):748-58.
Immunity to MCA-induced rat sarcomas: analysis of in vivo and in vitro results.
Harmon RC, Clark EA, Reddy AL, Hildemann WH, Mullen Y.
Three in vivo techniques were used to establish the specificity of tumor immunity induced after sensitization of F344 rats to syngeneic MCA-induced sarcomas: (1) post-excision resistance to tumor challenge, (2) passive tumor neutralization (the Winn test), and (3) concomitant immunity. In general, these assays revealed unique non-cross-reactive antigens associated with each of three sarcomas, FMF1, FMM2, and FMM3. However, spleen cells from tumor-sensitized rats did not demonstrate cell-mediated cytotoxicity in vitro corresponding to the specificity of tumor resistance in vivo. In the (3H)-proline cytotoxicity assay, spleen cells from FMM3 tumor-bearing rats or from FMM3 tumor-immune rats were not selectively cytotoxic for cultured FMM3 target cells. Parallel analysis of spleen cells from normal or FMM3-sensitized rats using the Winn assay and the (3H)-proline assay revealed that (1) spleen cell cytotoxicity in vitro did not correlate with effective tumor protection in vivo; and (2) normal spleen cells were cytotoxic against cultured sarcoma target cells in vitro and inhibited tumor growth in vivo. Thus, passive tumor protection by normal spleen cells in vivo corresponded with the demonstration of natural cytotoxicity in vitro, but induced specific anti-tumor reactivity was observed only in vivo.
So what happens if you do the same sort of experiments with a SPONTANEOUS cancer OF RECENT ORIGIN, a leukemia or a mammary carcinoma, for example? NOTHING.
Will it work? Certainly not be the mechanisms that they discuss, and that's what bugs me... they know damn well that every solid study known to man has failed to show the existence of tumor-specific antigens associated with spontaneous cancers. Srivastava's (IMO) story telling goes on and on, and somehow a company was built around it. To me, it's all very strange. You just don't go out and use a P815 or an EL4 or a meth-A and consider your work relevant to anything other than transplantation biology. They're old lab lines, and tell you about transplantation across non-major histocompatibility complex barriers, not about cancer therapy.
I worked, for six years, with induced and spontaneous cancers of recent origin. Large quantities of tumor cells were frozen after only one passage in the strain (mouse or rat) of origin, so that they would be RELEVANT models. Induced mouse and rat tumors were highly immunogenic, and that "antigenicity" could be demonstrated in a number of assays. Spontaneous cancers, however, do NOT induce the sort of response described in the paragraph (above) from AGEN.
It really disturbs me that they write this simplistic crap and pass it off as fact. Otherwise, I like Bob's suggestions. And, of course, I'm really hoping that chaperones work, by whatever mechanism. |
