April 2022: Secundum notitias praeliminares ex periodo I/II clinicae probationis quae in AACR Conventui Annui 2022 prolata est, quae ab 8-13 Aprilis habita erat, novum chimaericum antigenum receptaculum (CAR) T-cellae acceptum profile salutiferum habuit et ostendit signa prima efficaciae in monotherapia et in compositione cum variante vaccino in patientibus tumoribus solidis. Haec indicio allata sunt mense Aprili.
Applicatio autocinetorum car T-cellorum ad solidorum tumores difficilis esse probavit, obstante quod fundamentaliter mutaverit optiones medicinales in carcinomate hematologico prompti.
Secundum relatorem John Haanen, MD, PhD, oncologus medicinae in Instituto Nederlandiae Cancri (NKI), Amstelodami, Nederlandiae dixit "difficile esse proprie cellas CAR T contra tumores tumores dirigere, dum sanis parcens propter plurimas. servo praesentes in solidis tumoribus qui tamquam scuta adhiberi possunt etiam in parvis gradibus in cellulis normalibus inveniuntur". "Aliae provocationes includunt strictam perseverantiam CAR T cellularum in tumoribus solidis observatas", necnon "eorum difficultas tumores attingens et centrum massae penetrans", secundum art.
Ioannes Hannen . Dr
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-cell 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 orci iudicio 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 Lorem 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-cell 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 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.
"Mirum est quod plures aegros cum cancro testiculari ad dosis gradu 2 utilitatem clinicam demonstraverunt", dixit Haanen. "Responsiones quas animadvertimus possunt esse profundae, etiam una permanenti plenaria remissione."
Secundum Haanen, "infusio CLDN6 CAR T, sive sola sive coniuncta cum CARVac, tuta est et pollicetur aegris carcinomata CLDN6-positiva." "CLDN6 numquam iaculis ante cum therapiis cellularibus"; tamen, in studio nostro, aditus iam efficaciam ostendens quae melior sit quam notitia ex aliis CAR T iudiciis in solidis tumoribus, "inquisitores dixerunt.
Tamen, Haanen monuimus has notitias valde mature esse, et quia pauci ad hunc locum tractati sunt, immatura est ut quaslibet maiores conclusiones eligat.
Cognitio a subsidiaria comitatu BioNTech SE fundebatur quae BioNTech Cell & Gene Therapies GmbH erat. BioNTech subsidia oeconomica NKI ad eius investigationem praebebat. Societas BioNTech Haanen in tabula sua consiliaria scientifica ministrans habet. Merces pecuniaria ad NKI accedit.
Porro singula reprehendo in hic.
