Aprel 2022: 2022-8 aprel kunlari bo'lib o'tgan AACR yillik yig'ilishi 13da taqdim etilgan I/II klinik sinovning dastlabki ma'lumotlariga ko'ra, yangi kimerik antigen retseptorlari (CAR) T-hujayra mahsuloti maqbul xavfsizlik profiliga ega va ko'rsatilgan qattiq o'smalari bo'lgan bemorlarda monoterapiya sifatida va mRNK vaktsinasi bilan birgalikda samaradorlikning dastlabki belgilari. Ushbu ma'lumot aprel oyida taqdim etilgan.
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.
Taqdimotchi, MD, PhD, Niderlandiya saraton instituti (NKI) tibbiy onkologi Jon Xaanenning so'zlariga ko'ra, Amsterdam, Niderlandiya, "CAR T hujayralarini o'simta hujayralariga qarshi maxsus yo'naltirish qiyin, chunki sog'lom hujayralarni saqlash juda qiyin, chunki ko'pchilik maqsad sifatida ishlatilishi mumkin bo'lgan qattiq o'smalarda mavjud bo'lgan oqsillar oddiy hujayralarda ham past darajada topiladi. Maqolaga ko'ra, "Boshqa qiyinchiliklarga qattiq o'smalarda kuzatilgan CAR T hujayralarining cheklangan davom etishi", shuningdek, "ularning o'smalarga etib borishi va massa markaziga kirib borishi qiyinligi" kiradi.
Doktor Jon Xannen
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-hujayrasi 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 klinik tadqiqotlar 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-hujayra terapiyasi 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-hujayrasi 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 sitokinlarni chiqarish sindromi 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.
"Ajablanarlisi shundaki, moyaklar saratoni bilan og'rigan bemorlarning aksariyati 2-darajali dozada klinik foyda ko'rsatdi", dedi Xaanen. "Biz kuzatgan javoblar chuqur bo'lishi mumkin, shu jumladan davom etayotgan to'liq remissiya."
Haanenning so'zlariga ko'ra, "CLDN6 CAR T infuzioni yolg'iz yoki CARVac bilan birgalikda xavfsizdir va CLDN6-musbat saratoni bo'lgan bemorlar uchun va'da beradi." "CLDN6 hech qachon uyali terapiya bilan nishonlanmagan; ammo, bizning tadqiqotimizda, bu yondashuv qattiq o'smalarda boshqa CAR T sinovlari ma'lumotlariga qaraganda yaxshiroq bo'lishi mumkin bo'lgan samaradorlikni ko'rsatmoqda ", dedi tadqiqotchilar.
Biroq, Xaanen ogohlantirdiki, bu ma'lumotlar juda erta va shu paytgacha faqat oz sonli bemorlar davolanganligi sababli, biron bir muhim xulosa chiqarishga erta.
Tekshiruv BioNTech Cell & Gene Therapies GmbH nomi bilan tanilgan BioNTech SE sho'ba kompaniyasi tomonidan moliyalashtirilgan. BioNTech tadqiqoti uchun NKI ga moliyaviy yordam ko'rsatdi. BioNTech kompaniyasining ilmiy maslahat kengashida Haanen ishlaydi. Moliyaviy kompensatsiya NKIga o'tadi.
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