Afrilu 2022: Dangane da bayanan farko daga gwajin asibiti na lokaci I/II wanda aka gabatar yayin taron shekara-shekara na AACR 2022, wanda aka gudanar daga Afrilu 8-13, sabon samfurin T-cell na chimeric antigen (CAR) yana da ingantaccen bayanin martaba kuma ya nuna. alamun farko na inganci azaman monotherapy kuma a haɗe tare da maganin mRNA a cikin marasa lafiya masu ciwon ciwace-ciwace. An gabatar da wannan bayanin a watan Afrilu.
Aiwatar da maganin CAR T-cell zuwa ƙwararrun ciwace-ciwace ya tabbatar da cewa yana da wahala, duk da cewa ya canza ainihin zaɓuɓɓukan jiyya da ke akwai don cututtukan cututtukan jini.
A cewar mai gabatarwa, John Haanen, MD, PhD, masanin ilimin likitancin likita a Cibiyar Cancer ta Netherlands (NKI), Amsterdam, Netherlands, ya ce, "yana da wuya a musamman jagorantar kwayoyin CAR T a kan kwayoyin tumo yayin da ake kiyaye masu lafiya saboda yawancin sunadaran da ke kan ƙwararrun ciwace-ciwace waɗanda za a iya amfani da su azaman hari kuma ana samun su a ƙananan matakan akan sel na yau da kullun”. "Sauran ƙalubalen sun haɗa da iyakancewar dagewar ƙwayoyin CAR T da aka gani a cikin ƙwararrun ciwace-ciwacen daji," da kuma "wahalarsu ta kai ga ciwace-ciwacen daji da shiga tsakiyar taro," in ji labarin.
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 TAR 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 gwajin gwaji 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 CAR T-cell far 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 TAR 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 saki ciwo 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.
"Abin mamaki ne cewa yawancin marasa lafiya da ke fama da ciwon daji na jini sun nuna fa'idar asibiti a matakin kashi 2," in ji Haanen. "Amsoshin da muka lura na iya zama masu zurfi, gami da cikakkiyar gafara daya gudana."
A cewar Haanen, "Jikodin CLDN6 CAR T, ko dai shi kaɗai ko a hade tare da CARVac, ba shi da lafiya kuma yana da alƙawari ga majiyyata masu cutar kansa na CLDN6." “Ba a taɓa yin niyya da CLDN6 ba tare da maganin salula; duk da haka, a cikin bincikenmu, wannan tsarin ya riga ya nuna inganci wanda zai iya zama mafi kyau fiye da bayanan da aka samu daga wasu gwaje-gwajen CAR T a cikin ciwace-ciwacen ƙwayar cuta, "in ji masu binciken.
Duk da haka, Haanen ya yi gargadin cewa waɗannan bayanan sun kasance da wuri sosai, kuma saboda ƙananan marasa lafiya ne kawai aka yi musu magani har zuwa wannan lokacin, yana da wuri don yanke duk wani babban matsayi.
Wani kamfani na BioNTech SE wanda aka sani da BioNTech Cell & Gene Therapies GmbH ne ya dauki nauyin binciken. BioNTech ta ba da tallafin kudi ga NKI don bincikenta. Kamfanin BioNTech yana da Haanen yana aiki a hukumar ba da shawara ta kimiyya. Kudin diyya ya tafi NKI.
Duba ƙarin cikakkun bayanai akan nan.
