2022 April: Numutkeun data awal tina uji klinis fase I / II anu ditepikeun nalika Rapat Taunan AACR 2022, anu diayakeun ti 8-13 April, produk sél T-réséptor antigen antigen (CAR) chimeric anyar ngagaduhan profil kaamanan anu tiasa ditampi sareng nunjukkeun. tanda-tanda awal khasiat salaku monoterapi sareng digabungkeun sareng vaksin mRNA dina pasien kalayan tumor padet. Inpo ieu dibere dina April.
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.
Numutkeun presenter, John Haanen, MD, PhD, a onkologi médis di Institute Kanker Walanda (NKI), Amsterdam, Walanda ngomong, "hésé husus ngarahkeun sél T CAR ngalawan sél tumor bari sparing nu cageur sabab lolobana protéin nu aya dina tumor padet nu bisa dipaké salaku target ogé kapanggih dina tingkat low dina sél normal". "Tantangan sanésna kalebet kegigihan kawates sél T CAR anu dititénan dina tumor padet," ogé "kasusahna ngahontal tumor sareng nembus pusat massa," numutkeun tulisan éta.
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 CAR T-sél 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 sidang klinis 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 Terapi sél T-mobil 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 CAR T-sél 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 sindrom sékrési sitokin 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.
"Éta pikaheraneun yén seuseueurna pasien kanker testis nunjukkeun kauntungan klinis dina tingkat dosis 2," saur Haanen. "Tanggapan anu kami perhatikeun tiasa jero, kalebet hiji remisi lengkep."
Numutkeun kana Haanen, "The infusion of CLDN6 CAR T, boh nyalira atanapi dina kombinasi kalayan CARVac, aman tur nahan jangji pikeun penderita kanker CLDN6-positip." "CLDN6 ieu pernah sasaran saméméh kalayan terapi sélular; kumaha oge, dina ulikan urang, pendekatan ieu geus némbongkeun efficacy nu bisa jadi leuwih hade tinimbang data ti percobaan CAR T sejenna dina tumor padet, "ceuk peneliti.
Tapi, Haanen ngingetkeun yén data ieu awal pisan, sareng kusabab ngan sajumlah leutik pasien anu dirawat dugi ka titik ieu, éta prématur pikeun narik kasimpulan utama.
Panaliti ieu dibiayaan ku anak perusahaan BioNTech SE anu katelah BioNTech Cell & Gene Therapies GmbH. BioNTech nyayogikeun dukungan kauangan ka NKI pikeun panalungtikanana. Pausahaan BioNTech boga Haanen porsi dina dewan piwuruk ilmiah na. Santunan kauangan ka NKI.
Pariksa rinci salajengna leuwih Ieuh.
