BETA - Is the process of using TCR and CAR-T cells similar? What is the difference between a CAR-T and a TCR-T?

Is the process of using TCR in CAR T cells similar? The process of preparing patients to receive TCRT or CAR T is very similar. You collect the cells through aphoresis. You go through the transduction and the manufacturing process to prepare the cells, which takes around three to four weeks or so. Then once the cells are manufactured, you give the patient chemotherapy, so-called lympho-depleting chemotherapy to prepare their bodies to receive these TCR or CAR T cells, and then they are infused. Then the patient is observed typically in the hospital for a period of time to look for side effects like the cytokine release syndrome and the neurologic toxicity. The difference between a CAR T and a TCRT is that the T cell in the case of a CAR T is genetically modified or engineered to express a CAR, which stands for chimeric antigen receptor, which is really a freak of nature. It doesn't exist in nature. It's a combination molecule that is not found normally in nature, consists of an antibody on the outside and a T cell or immune cell signaling complex or domain on the inside. Basically, the antibody on the outside recognizes or attaches to the myeloma cell and then exerts a change in the molecular structure that then causes the T cell component or T cell part to deliver signals into the T cell to activate it and to induce expansion and proliferation. Whereas a TCR is really using nature's own molecular system for recognizing foreign invaders, whether they be germs or cancer. This is what the normal T cells in the body use, which is a T cell receptor, TCR, which itself recognizes the component of the germ or component of the cancer cell and then sends the signal into the T cell to activate and expand and proliferate. That's more of the natural way that T cells work and get activated. The difference is that the T cell or the TCR is specifically selected to recognize the cancer. We're not depending on the body's immune system to locate or find a small population of T cells or immune cells that can attack the myeloma. We're providing that to the T cell. That T cell receptor has already been identified as being a cancer specific and myeloma specific molecule, one that's capable of recognizing the tumor associated molecular features. Then we're providing that immune cell to the patient with the specific TCR, T cell receptor that's able to recognize the myeloma. We're not leaving it up to chance, if you will. We're providing that specific T cell with that specific T cell receptor that is already known to be able to recognize certain myeloma types and attack them. One of the differences between the CARs and the TCRs is that the CARs, because it has an antibody on the outside, that has to recognize something on the surface, typically a protein or an antigen on the surface of the myeloma cell. The current FDA approved CARs for myeloma recognize something called BCMA. The TCR actually recognizes a small peptide or a small sequence of amino acids that are expressed on the surface of the myeloma cell in the context of what's called an HLA molecule. The human leukocyte antigen, which is basically there to express internal antigens or internal proteins, whereas the CARs really primarily looking for external proteins, the TCR can potentially target internal antigens or internal tumor associated or myeloma associated antigens or proteins. However, these have to be broken up into little pieces before they are conveyed and expressed on the surface of the cell.