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Msg  25205 of 25547  at  10/27/2021 11:45:52 AM  by


The following message was updated on 10/27/2021 11:59:02 AM.

Competitors in TCR-T -- Iova, Intellia, TCRR and Timmunity

TIL therapy into phase 2 against metastatic melanoma, non-small cell lung cancer, head and neck cancers. In the absence of success against solid cancers, TIL may prove to be a first mover in ACT.

Trials employ resected tumors shipped to isolate and grow TILs which are infused and followed up with up to six infusions of IL-2 to expand and enhance a durable response. Cohorts of the trial include a follow on with Keytruda, a checkpoint inhibitor and, a fourth cohort to include additional TIL therapy possible if the first infusion is not achieving an expected result.

Safety: 54% grade 3 or 4 degradation of blood platelets. 56% grade 3 or 4 anemia, drop in red blood cells. Efficacy: N=66, 21% partial response, 2% complete response.

Nov 2018 Comment by Dr. Rosenberg -- https://www.aacr.org/professionals/blog/3944-2-til-therapy . Because TCR T-cell therapy utilizes peripheral lymphocytes, this represents an advantage over TIL therapy, he said. Peripheral lymphocytes can be a lot more active and have a higher proliferative potential compared to TILs that have been repetitively stimulated in a patient and have lost some of their ability to divide. If we could put these TCR genes into peripheral lymphocytes, many of whom are nave, these cells can have an explosive proliferative potential.
Amateur DEF: Nave Tcells are Tcells designs that are new out of the thymus gland and have not yet been assigned a mission ( e.g., as immune clean-outs, as cell killers, as memory cells on the watch, as effectors that call in the troops).

INTELLIA. While in the research stage, that is, while not not yet in murine research, their website identifies their objective in allogeneic therapies to treat solid tumors: >> We seek to leverage CRISPR/Cas9 genome editing to create next-generation engineered cells that can treat oncological and immunological diseases for which there are currently limited to no treatment options available. <<

My difficulty with using CRSPR in general is the concern over random, off-target gene changes. While cited in a handful of published papers, I was particularly struck that a company invented a machine to help identify unwanted gene changes near the location of the infusion. The following website is a advertisement for purchase. NOTE the second to last paragraph (paragraph begins with, For now, Kemic ") - the machine does not find unintended alterations outside of the infusion location.

https://phys.org/news/2021-02-crispr-app-reveals-unintended-mutations.amp#referrer=https://www.google.com&_tf=From %1$s

TCRR. Phase one targeting mesothelin-overexpression, which is associated with approximately 80,000 cancers in the US each year. Mesothelin cells are present in the heart, peritoneum and the lung. Utilizing ex vivo manufacturing. Phase one result in efficacy, as of June, 2021 is a 31% ORR.

TMMUNITY Therapeutic is tied into U Penn and has six CAR-Ts focusing upon solid cancers. Only one is in phase one trial. They have a TCR-T targeting the neoantigen NY-ESO-1 for a small, devastating cancer target, pontine glioma (where the spine and the brain meet). The potential for using a CAR-T in solid cancers is questionable. From memory of our Ziopharm R&D day, even Dr. June (of U. Penn.) acknowledged the limitation of utilizing CAR-T in solid cancers.

I am not concerned yet about these four competitors. I say YET if only because of the speed of innovation and the large count of bright minds chasing solid cancer solutions. As a for instance, CRISPR will likely find a way to eliminate the unintended and random cuts of the genome. The CEO of Sangamo publicly stated that he also expects this improvement in precision, just not very soon. I guess the FDA chooses an elevated risk/reward path when reviewing therapies for unmet, genetic diseases. Intellia recently provided positive, small patient count, early clinical result in SCD (sickle cell disease), yet they also used CRSPR tech for the gene editing required in that target. All the best.

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Msg # Subject Author Recs Date Posted
25206 Re: Competitors in TCR-T -- Iova, Intellia, TCRR and Timmunity clsm 1 10/27/2021 5:06:43 PM
25207 Re: Competitors in TCR-T -- Iova, Intellia, TCRR and Timmunity dnmun 6 10/28/2021 12:17:24 AM

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