Can someone more knowledgeable on the subject please clarify if this proposed therapy requires personalization for each patient or if it can be (eventually) mass produced? Thanks!
There are two kinds of personalization in a [CAR] [T] therapy:
1) using the patient's own cells [personalization of T Cells]
2) customized therapeutic genetic payload, per patient [personalization of the CAR]
There are current competing factions for #1 - where cells are from just the patient ["Autologous"] (safer, slower, more expensive), and where the cells are from a universal donor ["Allogeneic"] (possible immune response, but can be manufactured at scale).
The therapeutic payload is a DNA sequence encoding a synthetic chimeric receptor ["CAR"]. This sequence is customized based on the details of the patient's particular cancer, but are common across many people. If the cancer has an excess of "Protein X" on it, then the CAR sequence is designed to target Protein X. All patients with a similar cancer profile receive the same CAR sequence as a payload to the T cells. This too could be personalized, to not just profile the _class_ of cancer, but particular to that _specific patent's cancer's profile_ - but this is not yet feasible given the turnaround time to build, test and evaluate a new genetic payload in the context of a person's specific tumor cells.
This particular therapy has the cells be from the patient (personalized), but the CAR sequence provided to the cells is common for all people that have the same cancer profile (semi-personalized). In this case, the cancer profile includes those that have an abundance of the protein called Claudin-6.
chromatin|2 years ago
- banks of products with major HLA types, so that some matching is still required, but you don't need a 1:1 donor as with bone marrow transplant
- stripping, downregulation, or ablation of proteins that coudl cause rejection (eg HLA class II)
- expression of other tolerance signals
Here is a brief editorial on a paper using some of these stratgies: https://www.nature.com/articles/s41422-022-00745-4
Here is a more comprehensive review article: https://ehoonline.biomedcentral.com/articles/10.1186/s40164-...
jessriedel|2 years ago
jfarlow|2 years ago
1) using the patient's own cells [personalization of T Cells]
2) customized therapeutic genetic payload, per patient [personalization of the CAR]
There are current competing factions for #1 - where cells are from just the patient ["Autologous"] (safer, slower, more expensive), and where the cells are from a universal donor ["Allogeneic"] (possible immune response, but can be manufactured at scale).
The therapeutic payload is a DNA sequence encoding a synthetic chimeric receptor ["CAR"]. This sequence is customized based on the details of the patient's particular cancer, but are common across many people. If the cancer has an excess of "Protein X" on it, then the CAR sequence is designed to target Protein X. All patients with a similar cancer profile receive the same CAR sequence as a payload to the T cells. This too could be personalized, to not just profile the _class_ of cancer, but particular to that _specific patent's cancer's profile_ - but this is not yet feasible given the turnaround time to build, test and evaluate a new genetic payload in the context of a person's specific tumor cells.
This particular therapy has the cells be from the patient (personalized), but the CAR sequence provided to the cells is common for all people that have the same cancer profile (semi-personalized). In this case, the cancer profile includes those that have an abundance of the protein called Claudin-6.
f6v|2 years ago