It was all over the news (March 29, 2018) that a new cancer “vaccine” was about

Question

It was all over the news (March 29, 2018) that a new cancer “vaccine” was about to begin human trials after a 97% success rate in mouse trials against both blood cancers (lymphomas) and solid tumors such as breast and colon cancer. I will excerpt a description compiled from several scientific and news sources. Based on what we talked about in Bio 221, you should be able to understand this. Answer each of the questions about this exciting new “vaccine.” T cells are present in most tumors by infiltration. These include CTLA4-expressing Treg cells, as well as CD4- expressing TH cells and CD8-expressing cytotoxic T-lymphocytes. Once cancer is well established, the balance between these inputs is tipped toward immunosuppression. We found that a Toll-like receptor 9 (TLR9) ligand, CpG, induces the expression of OX40, an alternate costimulatory receptor, on CD4 T cells when it is injected into the tumor microenvironment. This is an indirect induction, in which CpG induces cytokine secretion by myeloid cells which in turn induces OX40 expression on T cells. Then OX40 can be activated using anti-OX40 antibodies, thereby activating TH cells in the tumor.

D. How do antibodies that recognize OX40 help to stimulate TH cells? (Hint: think about autoimmune diseases. There is one we didn’t talk about, called Graves’ disease, that you might want to look up, too.) What else is required for the TH cells to become activated?

E. How does all of this kill the cancer cells? What other cells in the tumor also must become activated? How?

F. How does this differ from the CAR-T cell therapy?

Explanation / Answer

D.

Antibody recognizing OX40 help in stimulating the T cell with the help of antibody dependent T cell activation. Antibody with OX40 binds to receptor for signal 2 on TH cell and provide the costimulatory signal or signal 2 to activate the TH cells. TH cells also required signal 1 coming directly from the APCs.

E.

The activated TH cells release the certain cytokines like TNF etc that directly act upon the tumor to kill them. Other cells like macrophages and B cells for producing the antibody need to be activated.

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