Abril 2022: Ayon sa paunang data mula sa isang phase I/II na klinikal na pagsubok na ipinakita sa panahon ng AACR Annual Meeting 2022, na ginanap mula Abril 8-13, isang bagong chimeric antigen receptor (CAR) T-cell na produkto ay may katanggap-tanggap na profile sa kaligtasan at nagpakita maagang mga palatandaan ng pagiging epektibo bilang isang monotherapy at kasama ng isang bakunang mRNA sa mga pasyente na may mga solidong tumor. Ang impormasyong ito ay ipinakita noong Abril.
The application of CAR T-cell therapy to solid tumours has proven to be difficult, despite the fact that it has fundamentally altered the treatment options available for hematologic cancers.
Ayon sa nagtatanghal, si John Haanen, MD, PhD, isang medikal na oncologist sa Netherlands Cancer Institute (NKI), Amsterdam, Netherlands ay nagsabi, "mahirap na partikular na idirekta ang mga selulang CAR T laban sa mga selula ng tumor habang pinipigilan ang mga malusog dahil karamihan sa ang mga protina na naroroon sa mga solidong tumor na maaaring gamitin bilang mga target ay matatagpuan din sa mababang antas sa mga normal na selula". "Kabilang sa iba pang mga hamon ang limitadong pagtitiyaga ng mga selulang CAR T na naobserbahan sa mga solidong tumor," gayundin ang "kahirapan nilang maabot ang mga tumor at tumagos sa gitna ng masa," ayon sa artikulo.
Dr. John Hannen
Haanen and colleagues are conducting a first-in-human, open label, multicenter clinical trial to evaluate the safety and preliminary efficacy of a previously developed T-cell ng CAR product that targets CLDN6. CLDN6 is a tumor-specific antigen that is widely expressed in a variety of solid tumours but is silenced in healthy adult tissues. The purpose of this klinikal na pagsubok is to determine whether or not the product is safe to use in humans and to determine whether or not it has preliminary therapeutic potential. This treatment was evaluated in preclinical models in conjunction with a CLDN6-encoding mRNA vaccine known as CARVac, which promotes the growth of CAR T cells. According to Haanen’s explanation, this combined treatment, which is known as BNT211, led to an increase in the transferred CAR T cells’ capacity to multiply and their persistence in the blood, which, in turn, led to an improvement in the ability to kill tumour cells.
Patients with relapsed or refractory advanced CLDN6-positive solid tumours were sought out by the researchers in order to test the effectiveness of the CLDN6 Therapy ng T-cell ng CAR both on its own and in conjunction with CARVac.
Following lymphodepletion to reduce the total number of T cells present in the body and make room for the transferred CAR T cells, the clinical trial was divided into two parts. In the first part, increasing doses of CLDN6 CAR T cells were administered as monotherapy. In the second part, the same treatment was administered in combination with CARVac. In Part 2, CARVac was given to the patient every two to three weeks for the first one hundred days after the T-cell ng CAR transfer. Additionally, one patient received maintenance vaccinations every six weeks. When this report was written, a total of 16 patients had been treated up to that point.
A manageable cytokine release syndrome developed in approximately forty percent of patients, but there was no evidence of neurotoxicity in any of these patients. Cytopenia, also known as a low blood cell count, and abnormal immune responses were some of the other adverse events that occurred, but they all went away on their own. After receiving CARVac, some people experienced fleeting symptoms similar to the flu that lasted for up to 24 hours. According to Haanen, “CLDN6 CAR T treatment and CARVac seemed to be safe, with only a limited number of adverse events that were easily manageable.”
Four patients with testicular cancer and two patients with ovarian cancer experienced a partial response (PR) at six weeks after infusion, resulting in an overall response rate of nearly 43 percent. The patients who were evaluable for efficacy were divided into two groups: those who had testicular cancer and those who had ovarian cancer. Among the people who took part in the research and had a PR, there were two patients who were treated with the combination of CAR T cells and CARVac and four patients who received CAR T cells as a monotherapy. There was an 86% success rate in eradicating the disease. At 12 weeks after the infusion, it was found that initial partial responses had improved in all of the patients who could be evaluated. This led to a single complete response, which is still present six months after the infusion was given.
"Nakakagulat na ang karamihan ng mga pasyente na may kanser sa testicular ay nagpakita ng klinikal na benepisyo sa antas ng dosis 2," sabi ni Haanen. "Ang mga tugon na naobserbahan namin ay maaaring maging malalim, kabilang ang isang patuloy na kumpletong pagpapatawad."
Ayon kay Haanen, "Ang pagbubuhos ng CLDN6 CAR T, nag-iisa man o kasama ng CARVac, ay ligtas at may pangako para sa mga pasyenteng may CLDN6-positive cancers." "Ang CLDN6 ay hindi kailanman na-target dati ng cellular therapy; gayunpaman, sa aming pag-aaral, ang pamamaraang ito ay nagpapakita na ng pagiging epektibo na maaaring mas mahusay kaysa sa data mula sa iba pang mga pagsubok sa CAR T sa mga solidong tumor, "sabi ng mga mananaliksik.
Gayunpaman, binalaan ni Haanen na ang mga datos na ito ay napakaaga, at dahil kakaunti lamang ang bilang ng mga pasyente na nagamot hanggang sa puntong ito, napaaga na gumawa ng anumang malalaking konklusyon.
Ang pagsisiyasat ay pinondohan ng subsidiary na kumpanya ng BioNTech SE na kilala bilang BioNTech Cell & Gene Therapies GmbH. Nagbigay ang BioNTech ng suportang pinansyal sa NKI para sa pananaliksik nito. Ang kumpanyang BioNTech ay may Haanen na nagsisilbi sa siyentipikong advisory board nito. Ang kabayaran sa pananalapi ay napupunta sa NKI.
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