Sunday, May 8, 2016

TIL - Tumor infiltrating lymphocytes

I haven't put up a great deal about TIL therapy.  It is a complicated and somewhat risky process.  Selection if often very exclusive...partly because it can be a very tough treatment....and partly due to (in my mind) the desire for some of the institutions who provide it to skew their results into a more impressive report through selection of the 'best' candidates. 
But, again for dear Josh (and the rest of you in need) I am putting together some information as best I can.  Here we go....

In this post from 2013:  Ode to Pati  I said.......

"What is TIL?  TIL (Tumor infiltrating lymphocytes) are used in an ACT (adoptive cell transfer) therapy like this:  A tumor is removed from the patient's body.  Lymphocytes are collected from it.  Those lymphocytes are tested in order to identify the cells that show the greatest anti-tumor activity.  Then....those particular cells are grown in a lab for several weeks.  If the TIL cells grow sufficiently, the patient is given a body pounding dosing of chemotherapy to rid the body of other lymphocytes so that the new TIL batch will be accepted more readily when they are infused with no other immune cells there to attack them.  The newly grown lymphocytes are then returned to the patient in an infusion along with a cytokine (immune stimulating agent) like IL2 (interleukin 2).  In numerous studies TIL demonstrates a 50% response rate in patients with metastatic melanoma."

So....basically.  A tumor is harvested.  T-cells are extracted from it...with the idea that they were good soldiers who had already recognized and were in the process of attacking that tumor.  To increase their numbers...they are grown in a dish.  To further their interests...the patient (ie the battlefield) is injected with bad stuff (IL-2, IL-21, or cyclophosphomide and fludarabine, are frequently used) to kill off T-cells that might try to block their fight with the tumor...and/or support the good T-cells...which are then sent back into battle (ie injected into the patient)!

Here's the Wiki version...which is pretty good:  wiki: Adoptive cell transfer

Here is a recent post about a new TIL study that is recruiting:  TIL: tumor infiltrating lymphocytes

Now....the nifty thing that is happening in TIL therapy that researchers are genetically modifying the t-cells they harvest from the tumor to make them even better at recognizing, attacking, and killing the tumors in question.  There are several different ways they are doing this and it is all rather complicated...but super cool.

In the study being considered:  Transfer of genetically engineered lymphocytes in melanoma patients
Here's the deal: This trial was started in 2012.  There are 4 cohorts with 4 dosing levels.  Not sure where they are in that process at this moment.   You get one infusion of TIL with low dose IL2.  You have to be "positive for both tyrosinase and HLA-A2" per biopsy and pass their heart test.  If you've had ipi, you have to be 3 months post last dose.  If BRAF positive you have to have failed Vemurafenib or been offered Vemurafenib and declined. This exclusion is present:  "Patients that have undergone immunotherapy in combination with non-myeloablative chemotherapy." Various lab values have to be in normal ranges.  It is offered at Loyola.

Here is an old report from 2006:  Cancer regression in patients after transfer of genetically engineered lymphocytes.  It notes that of 15 patients treated at that point, 2 durable response were attained.  Generally 50% of TIL patients gain a durable response...remembering we are talking about a select group.  At the end of the article (which is available as a PDF file) it says:  "In human subjects, normal autologous T lymphocytes, transduced ex vivo with anti-TAA–TCR genes and reinfused in cancer patients, can persist and express the transgene for a prolonged  time in vivo and mediate the durable regression of large established tumors. Although the response rate (2 out of 15 patients or 13%) seen in cohorts 2 and 3 is lower than that achieved by the infusion of autologous TILs (50%), this method has potential for use in patients for whom TILs are not available."

A complicated bunch of mess....but there you go. - c


  1. Celeste-really confused on the Genetically modified T Cells from the there good response? Doesn't seem like data and what my docs feel is a great option for me right now. I know MDA has the TIL....should I be looking at that. Decisions, decisions....decisions. Still great info...again thank you!!!


  2. It's all pretty crazy. All I can think to do if I were in your talk to the docs you're about to meet and ask all the questions you have. The type of TIL your trial in question embarks on is pretty new....and the data is just not there yet. You would be the rattie telling the tail!!!! on that one! Then...after getting all the'll just have to go with what feels right and best for you. I know that's not a great answer...but I've been in a quandary before and that's what I had to do. Wish we weren't so much uncharted territory! Hang in there. love, c