April 2022: Ngokwedatha yokuqala evela esivivinyweni somtholampilo sesigaba I/II esethulwa phakathi Nomhlangano Wonyaka we-AACR 2022, owawungo-Ephreli 8-13, umkhiqizo omusha we-chimeric antigen receptor (CAR) T-cell wawunephrofayela eyamukelekayo yokuphepha futhi uyaboniswa. izimpawu zakuqala zokusebenza ngempumelelo njenge-monotherapy kanye nokuhlanganiswa nomgomo we-mRNA ezigulini ezinezicubu eziqinile. Lokhu kwaziswa kwethulwe ngo-April.
Ukusetshenziswa kokwelashwa kwe-CAR T-cell kumathumba aqinile kubonakale kunzima, naphezu kweqiniso lokuthi kuguqule ngokuyisisekelo izindlela zokwelapha ezitholakalayo zomdlavuza we-hematological.
Ngokusho komethuli, uJohn Haanen, MD, PhD, udokotela oncologist wezokwelapha eNetherlands Cancer Institute (NKI), Amsterdam, Netherlands uthe, "kunzima ukuqondisa ngokuqondile amangqamuzana e-CAR T ngokumelene namangqamuzana e-tumor ngenkathi usindisa anempilo ngoba iningi amaprotheni akhona kumathumba aqinile angasetshenziswa njengezinhloso nawo atholakala emazingeni aphansi kumaseli avamile”. “Ezinye izinselele zihlanganisa ukuphikelela okulinganiselwe kwamangqamuzana e-CAR T abonwa ezimila eziqinile,” kanye “nobunzima bawo bokufinyelela izimila nokungena phakathi nendawo,” ngokwalesi sihloko.
UDkt. 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 ISITOLO SEZIMOTO 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 isivivinyo somtholampilo 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 Ukwelashwa kwe-CAR T-cell 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 ISITOLO SEZIMOTO 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 i-cytokine release syndrome 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.
“Kuyamangaza ukuthi iningi leziguli ezinomdlavuza wamasende zikhombise ukuhlomula emtholampilo ezingeni lesi-2,” kusho uHaanen. "Izimpendulo esizibonile zingaba zinkulu, okuhlanganisa nokuxolelwa okuphelele okuqhubekayo."
NgokukaHaanen, “Ukuthelwa kwe-CLDN6 CAR T, kungaba iyodwa noma kuhlanganiswe ne-CARVAc, kuphephile futhi kunesithembiso ezigulini ezinomdlavuza we-CLDN6-positive.” “I-CLDN6 yayingakaze iqondiswe ngaphambili ngokwelashwa ngamaselula; kodwa-ke, ocwaningweni lwethu, le ndlela isivele ikhombisa ukusebenza kahle okungenzeka kube ngcono kunedatha evela kwezinye izivivinyo ze-CAR T kumathumba aqinile,” kusho abacwaningi.
Kodwa-ke, u-Haanen uxwayise ngokuthi le datha isheshe kakhulu, futhi ngenxa yokuthi inani elincane kuphela leziguli eselashwe kuze kube manje, kusengaphambi kwesikhathi ukwenza noma yiziphi iziphetho ezinkulu.
Uphenyo beluxhaswe yinkampani engaphansi kwe-BioNTech SE eyaziwa nge-BioNTech Cell & Gene Therapies GmbH. I-BioNTech inikeze i-NKI ukwesekwa kwezimali ngocwaningo lwayo. Inkampani i-BioNTech inoHaanen osebenza ebhodini lakhe lokweluleka ngokwesayensi. Isinxephezelo sezezimali siya ku-NKI.
Bheka imininingwane eyengeziwe lapha.
