April 2022： 2022月8日から13日まで開催されたAACR年次総会XNUMXで発表された第I/II相臨床試験の予備データによると、新しいキメラ抗原受容体（CAR）T細胞製品は許容可能な安全性プロフィールを有し、固形腫瘍患者における単独療法および mRNA ワクチンとの併用療法としての有効性の初期の兆候。 この情報はXNUMX月に発表されました。
CAR T細胞療法を固形腫瘍に適用することは、血液がんに利用可能な治療選択肢を根本的に変えたという事実にもかかわらず、困難であることが判明している。
発表者によると、オランダのアムステルダムにあるオランダがん研究所（NKI）の腫瘍内科医であるジョン・ハーネン医師は次のように述べています。標的として使用できる固形腫瘍に存在するタンパク質は、正常細胞にも低レベルで存在します。」 記事によると、「その他の課題としては、固形腫瘍で観察されるCAR T細胞の持続性が限られていること」や、「腫瘍に到達して塊の中心に侵入することが難しいこと」が挙げられる。
ジョン・ハンネン博士
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 CART細胞 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 臨床試験 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 CART細胞療法 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 CART細胞 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 サイトカイン放出症候群 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.
「精巣がん患者の大部分が用量レベル 2 で臨床的利益を示したことは驚くべきことです」と Haanen 氏は述べた。 「私たちが観察した反応は、進行中の完全な寛解を含め、深刻なものになる可能性があります。」
Haanen 氏によると、「CLDN6 CAR T の注入は、単独でも、CARVac と組み合わせても安全であり、CLDN6 陽性がん患者にとって有望です。」 「CLDN6 は、これまで細胞療法で標的にされたことはありませんでした。 しかし、私たちの研究では、このアプローチは、固形腫瘍における他のCAR T試験のデータよりも優れている可能性がある有効性をすでに示しています」と研究者は述べています.
ただし、ハーネン氏は、これらのデータは非常に初期のものであり、これまでに少数の患者しか治療されていないため、主要な結論を引き出すのは時期尚早であると警告しました.
この調査は、BioNTech Cell & Gene Therapies GmbH として知られる BioNTech SE の子会社によって資金提供されました。 BioNTech は、NKI の研究に財政的支援を提供しました。 BioNTech という会社では、Haanen が科学諮問委員会のメンバーを務めています。 金銭的補償は NKI に支払われます。
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