ABSTRACTS: CT002, CT003
SAN DIEGO ― Researchers from The College of Texas MD Anderson Most cancers Heart offered encouraging findings at this time from two medical trials in a plenary session highlighting advances in novel immunotherapy approaches on the American Affiliation for Most cancers Analysis (AACR) Annual Assembly 2024. The research describe the usage of chimeric antigen receptor (CAR) T cell remedy in sufferers with superior kidney most cancers and an oncolytic immunotherapy for sufferers with pores and skin most cancers following organ transplants. Data on all MD Anderson AACR Annual Assembly content material may be discovered at MDAnderson.org/AACR.
Novel allogenic CAR T cell remedy reveals promising leads to sufferers with superior clear cell renal cell carcinoma (CT002)
Amongst sufferers with superior clear cell renal cell carcinoma (ccRCC) who have been handled with CTX130™, an allogeneic CAR T cell remedy, 81% skilled a medical profit, together with 75% with secure illness, and one participant who skilled a sturdy full response of greater than three years.
Outcomes from the COBALT-RCC examine have been offered at this time by Samer Srour, M.B.Ch.B., assistant professor of Stem Cell Transplantation & Mobile Remedy, and revealed concurrently in Most cancers Discovery, a journal of the AACR.
“Our trial presents the primary and the longest sturdy response we’ve seen with an allogeneic, off-the-shelf, CAR T cell remedy within the remedy of refractory strong tumors,” Srour stated. “These findings are thrilling and inspiring as we proceed to enhance remedy choices for sufferers with clear cell renal cell carcinoma and different high-risk strong tumors who in any other case have poor outcomes.”
On this Section I multi-center trial, researchers evaluated the security and efficacy of CTX130, which targets CD70, a tumor antigen current at excessive ranges in ccRCC. CD70 is understood to have a job within the suppressive immune tumor microenvironment attributable to T cell exhaustion and regulatory T cell enlargement, amongst different mechanisms.
Sufferers with metastatic ccRCC who don’t profit from present commonplace therapies have restricted remedy choices and a poor prognosis. CTX130 makes use of T cells from wholesome donors edited to focus on CD70 and to disrupt the TRAC and β2M genes, which ought to cut back graft vs. host illness and donor rejection.
The trial enrolled 16 sufferers with a median age of 63 years in 4 dose-level cohorts. Researchers discovered a suitable security profile and inspiring antitumor exercise with CTX130. Negative effects have been manageable.
The trial’s findings present a proof of idea, meriting additional exploration of CD70-targeted CAR T cell remedy in ccRCC and different CD70-positive cancers. Srour and his colleagues utilized findings from this trial to develop CTX131, which improves on CTX130, and at present are enrolling sufferers in a Section I/II medical trial (NCT05795595) to guage the brand new remedy.
The trial was sponsored by CRISPR Therapeutics. Srour reviews no related disclosures. A full listing of collaborating authors and their disclosures may be discovered with the total paper right here.
Oncolytic immunotherapy reveals anti-tumor exercise in pores and skin most cancers sufferers following organ transplant (Summary CT003)
Findings from the Section Ib/II ARTACUS examine, led by Michael Migden, M.D., professor of Dermatology, present that utilizing an oncolytic immunotherapy referred to as RP1, which is a modified herpes simplex virus (HSV-1), is an efficient remedy choice for strong organ transplant (SOT) recipients who’ve superior non-melanoma pores and skin most cancers.
The information revealed the RP1 monotherapy was nicely tolerated and achieved an goal response charge of 34.8% and an entire response charge of 21.7%.
“Organ transplant recipients face an elevated danger of non-melanoma pores and skin cancers, and the usual remedy consists of immune checkpoint inhibitors. Sadly, these therapies may cause rejection of the transplanted organ,” Migden stated. “Information from this examine recommend RP1 monotherapy presents a promising doable various for this susceptible affected person inhabitants.”
Oncolytic immunotherapy makes use of viruses to focus on and destroy most cancers cells whereas additionally stimulating the physique’s immune response towards the tumor. The viruses are modified to allow them to selectively infect and replicate inside most cancers cells, resulting in their destruction.
The trial adopted 27 SOT recipients who had cutaneous squamous cell carcinoma or Merkel cell carcinoma and a median age of 68 years. Tumor biopsies have been collected for biomarker analyses and HSV-1 immune standing was monitored.
After RP1 remedy, participant tumor samples confirmed a rise in sure immune cells, referred to as CD8+ T cells, getting into the tumor, in addition to a lift within the manufacturing of the immune checkpoint protein PD-L1 throughout the tumor cells. This steered elevated anti-tumor immune activation.
Antagonistic results have been minimal, together with fatigue, chills and fever, and there was no proof of transplant rejection.
This examine was sponsored by Replimune. A full listing of collaborating authors and their disclosures may be discovered right here.
Learn this press launch within the MD Anderson Newsroom.
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