Nisan 2022: 2022-8 Nisan tarihleri arasında gerçekleştirilen AACR Yıllık Toplantısı 13 sırasında sunulan faz I/II klinik denemesinden elde edilen ön verilere göre, yeni bir kimerik antijen reseptörü (CAR) T hücresi ürünü kabul edilebilir bir güvenlik profiline sahipti ve gösterdi Katı tümörlü hastalarda monoterapi olarak ve mRNA aşısı ile kombinasyon halinde etkililiğin erken belirtileri. Bu bilgi Nisan ayında sunuldu.
Hematolojik kanserler için mevcut tedavi seçeneklerini temelden değiştirmiş olmasına rağmen, CAR T hücresi tedavisinin katı tümörlere uygulanmasının zor olduğu kanıtlanmıştır.
Sunucuya göre, Hollanda Kanser Enstitüsü (NKI), Amsterdam, Hollanda'da tıbbi onkolog olan John Haanen, MD, PhD şunları söyledi: "CAR T hücrelerini spesifik olarak tümör hücrelerine karşı yönlendirirken sağlıklı olanları korumak zordur çünkü çoğu Katı tümörlerde bulunan ve hedef olarak kullanılabilecek proteinler normal hücrelerde de düşük seviyelerde bulunuyor”. Makaleye göre "Diğer zorluklar arasında katı tümörlerde gözlemlenen CAR T hücrelerinin sınırlı kalıcılığı" ve "tümörlere ulaşma ve kütlenin merkezine nüfuz etme zorlukları" yer alıyor.
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 ARABA T-hücresi 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 deneme 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 hücre tedavisi 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 ARABA T-hücresi 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 sitokin salınım sendromu 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.
Haanen, "Testis kanseri olan hastaların çoğunluğunun 2. dozda klinik fayda göstermesi şaşırtıcı" dedi. "Gözlemlediğimiz tepkiler, devam eden tam bir iyileşme de dahil olmak üzere derin olabilir."
Haanen'e göre, "CLDN6 CAR T'nin tek başına veya CARVac ile kombinasyon halinde infüzyonu güvenlidir ve CLDN6 pozitif kanserli hastalar için umut vaat etmektedir." “CLDN6 daha önce hücresel terapiyle hiç hedef alınmamıştı; ancak bizim çalışmamızda bu yaklaşım, katı tümörlerde yapılan diğer CAR T çalışmalarından elde edilen verilerden daha iyi olabilecek etkinliği zaten gösteriyor" dedi araştırmacılar.
Ancak Haanen, bu verilerin çok erken olduğu ve bu noktaya kadar yalnızca az sayıda hasta tedavi edildiği için herhangi bir önemli sonuca varmak için henüz erken olduğu konusunda uyardı.
Araştırma, BioNTech SE'nin BioNTech Cell & Gene Therapies GmbH olarak bilinen yan şirketi tarafından finanse edildi. BioNTech, araştırması için NKI'ye mali destek sağladı. BioNTech şirketinin bilimsel danışma kurulunda Haanen görev yapıyor. Mali tazminat NKI'ye gider.
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