Prill 2022: Sipas të dhënave paraprake nga një provë klinike e fazës I/II që u prezantua gjatë Takimit Vjetor të AACR 2022, i cili u mbajt nga 8-13 Prill, një produkt i ri i qelizave T të receptorit kimerik të antigjenit (CAR) kishte një profil të pranueshëm sigurie dhe tregoi shenjat e hershme të efikasitetit si monoterapi dhe në kombinim me një vaksinë mRNA në pacientët me tumore të ngurta. Ky informacion u prezantua në prill.
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.
Sipas prezantuesit, John Haanen, MD, PhD, një onkolog mjekësor në Institutin Holandez të Kancerit (NKI), Amsterdam, Holandë tha, "është e vështirë të drejtosh në mënyrë specifike qelizat CAR T kundër qelizave tumorale duke kursyer ato të shëndetshme sepse shumica e proteinat e pranishme në tumoret e ngurta që mund të përdoren si objektiva gjenden gjithashtu në nivele të ulëta në qelizat normale”. “Sfida të tjera përfshijnë qëndrueshmërinë e kufizuar të qelizave CAR T të vërejtura në tumoret e ngurta, si dhe “vështirësinë e tyre për të arritur tumoret dhe për të depërtuar në qendër të masës”, sipas artikullit.
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 Qeliza T 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 gjykim klinik 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 Terapia me qeliza T 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 Qeliza T 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 sindromi i çlirimit të citokinës 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.
“Është befasuese që shumica e pacientëve me kancer testicular treguan përfitim klinik në nivelin e dozës 2,” tha Haanen. "Përgjigjet që kemi vëzhguar mund të jenë të thella, duke përfshirë një falje të plotë të vazhdueshme."
Sipas Haanen, "Infuzioni i CLDN6 CAR T, qoftë i vetëm ose në kombinim me CARVac, është i sigurt dhe premton për pacientët me kancer CLDN6 pozitiv". “CLDN6 nuk ishte shënjestruar kurrë më parë me terapinë qelizore; megjithatë, në studimin tonë, kjo qasje tashmë po tregon një efikasitet që mund të jetë më i mirë se të dhënat nga provat e tjera të CAR T në tumoret e ngurta, "thanë studiuesit.
Megjithatë, Haanen paralajmëroi se këto të dhëna janë shumë të hershme dhe për shkak se vetëm një numër i vogël pacientësh janë trajtuar deri në këtë pikë, është e parakohshme për të nxjerrë ndonjë përfundim të madh.
Hetimi u financua nga kompania degë e BioNTech SE e njohur si BioNTech Cell & Gene Therapies GmbH. BioNTech ka ofruar mbështetje financiare për NKI për kërkimin e saj. Kompania BioNTech ka Haanen që shërben në bordin e saj këshillues shkencor. Kompensimi financiar shkon për NKI.
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