A little about T-cells. I'm not a doctor, but I asked a lot of questions during and after the clinical trial.
Killer T-Cells (CD8+ cells) are a type of tumor-infiltrating lymphocyte. Each T-cell is designed to recognize one (and ONLY one) antigen (bad guy). The part of the T-cell doing the "recognizing" is the T-Cell receptor--each T-cell has thousands of receptors, all of them on a particular T-cell are programmed to recognize the same antigen.
T-cells become activated when they sense their target. Activated T-cells replicate themselves repeatedly, building up an army of killers that can wipe out invaders, even cancer.
An important aspect of Killer T-Cells (CD8+ cells) is that they can only recognize their target in the context of HLA. An HLA molecule has to essentially "hold onto" or "present" the T-Cell's target in order for the T-Cell to recognize it. When a doctor describes a mutation as "immunogenic
" it means that the person's immune system recognizes that antigen
Dr. Rosenberg's TIL trial (NCT01174121) requires surgery to remove a tumor. Why? Because they want to find THAT tumor's mutations, and to study THAT tumor's TIL. For trial NCT01174121 it makes no difference what HLA the patient has, nor what mutation. NCT01174121 uses the mutation and the HLA that is present in THAT patient. The key idea here is that the patient already has HLA and TIL that are fighting tumors.
The trial is concerned with identifying which HLA and which mutation are already there, then go multiply that specific population of T-cells (TIL) and give it back to the patient. The patient receives their own T-cells--with their own receptors-- back.
Dr. Yang's trial (NCT03190941
) does NOT require surgery to remove a tumor. Why? Because they already know what HLA and mutation worked in the mice. They intentionally studied mutations of RAS genes, and they used an HLA that they thought a high percentage of patients would carry (A*1101). Patients in this trial will get their own T-cells back, but the receptors on those T-cells will be from another source.
I hope this helps. Sneaky Tumor
is a blog post I wrote that might make things more clear about how HLA works.
my blog: Cancer RiotNED since April 2016!
April 2016: lower left lung lobectomy. NED
8 mo. f/u: 1 of 7 tumors progressed.
6 mo. f/u PR
confirmed (Jan 2016)
Jul 2015: NIH TIL trial NCT01174121 NCI/NIH Surgery Branch FAQ
Dec 2014 confirmed stage IV w/bilateral lung mets
FOLFOX + Radiation (bladder)
KRAS G12D :: MSS
dx Sep 2013 @47yo: IIIc T4b N2b MX [bladder invasion, 17/21 lymph nodes]
Married 28 yrs. kids: 24
SE Michigan home schooler, unemployed mechanical engineer, and programmer.