April 2022: Menurut data awal dari uji klinis fase I/II yang dipresentasikan selama Pertemuan Tahunan AACR 2022, yang diadakan dari 8-13 April, produk sel T chimeric antigen receptor (CAR) baru memiliki profil keamanan yang dapat diterima dan menunjukkan tanda-tanda awal kemanjuran sebagai monoterapi dan dalam kombinasi dengan vaksin mRNA pada pasien dengan tumor padat. Informasi ini disampaikan pada bulan 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.
Menurut presenter, John Haanen, MD, PhD, ahli onkologi medis di Netherlands Cancer Institute (NKI), Amsterdam, Belanda mengatakan, “sulit untuk secara spesifik mengarahkan sel T CAR melawan sel tumor sambil menyisihkan yang sehat karena sebagian besar protein yang ada pada tumor padat yang dapat digunakan sebagai target juga ditemukan pada tingkat rendah pada sel normal”. “Tantangan lain termasuk terbatasnya persistensi sel T CAR yang diamati pada tumor padat,” serta “kesulitan mereka mencapai tumor dan menembus pusat massa,” menurut artikel tersebut.
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 Sel T MOBIL 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 uji 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 sel-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 Sel T MOBIL 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 pelepasan 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.
“Sangat mengejutkan bahwa sebagian besar pasien dengan kanker testis menunjukkan manfaat klinis pada tingkat dosis 2,” kata Haanen. "Respons yang kami amati bisa sangat mendalam, termasuk satu remisi lengkap yang sedang berlangsung."
Menurut Haanen, "Infus CLDN6 CAR T, baik sendiri atau dalam kombinasi dengan CARVac, aman dan menjanjikan untuk pasien dengan kanker CLDN6-positif." “CLDN6 tidak pernah ditargetkan sebelumnya dengan terapi seluler; namun, dalam penelitian kami, pendekatan ini sudah menunjukkan kemanjuran yang mungkin lebih baik daripada data dari uji coba CAR T lainnya pada tumor padat,” kata para peneliti.
Namun, Haanen memperingatkan bahwa data ini masih sangat awal, dan karena hanya sejumlah kecil pasien yang telah dirawat hingga saat ini, terlalu dini untuk menarik kesimpulan besar.
Investigasi didanai oleh anak perusahaan BioNTech SE yang dikenal sebagai BioNTech Cell & Gene Therapies GmbH. BioNTech memberikan dukungan keuangan kepada NKI untuk penelitiannya. Perusahaan BioNTech memiliki Haanen yang bertugas di dewan penasihat ilmiahnya. Kompensasi finansial masuk ke NKI.
Periksa detail lebih lanjut di atas di sini.
