After the Spring Festival, good news came from cell ** one after another (such as the approval of the global TIL cell**-lifileucel and the fifth domestic CAR-T product-Zevogene autoleucel). So will there continue to be cell approvals this year? The answer is yes. Today, Kangheyuan Immunity Home will introduce to you the T cells** genetically engineered by cell receptors, namely TCR-T cells**.
About TCR-T
TCR-T cells** are also a type of adoptive cell metastasis** (ACT), which uses genetic engineering to modify T cells from the patient's peripheral blood by screening and identifying the TCR sequence that can specifically bind to the target antigen, and then infuses the modified T cells back into the patient's body, so that they can specifically recognize and kill the tumor cells expressing the antigen, so as to achieve the purpose of **tumor. T cell receptor engineered T cells** (TCR-T)** are not limited by the expression of antigens on the surface of target cells and are a potential immunodeficiency approach for tumor cells. It can be used in a wide range of malignant tumor cells, including solid tumors, and has also shown great potential in tumors.
About afami-cel
On January 31, Adaptimmune Therapeutics announced that the U.S. Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for its engineered T cell receptor (TCR) T cell** Afamitresgene Autoleucel (AFAMI-CEL) and granted priority review status. The target date for the application is August 4, 2024.
The BLA submission is based on positive data from Cohort 1 in a pivotal study, Spearhead-1. Data from the trial were presented at the 2023 Annual Meeting of the Society of Connective Tissue Oncology (CTOS). In the Spearhead-1 trial, the overall objective response rate (ORR) was approximately 39 percent. The median duration of response (DOR) of the product is approximately 12 months, indicating the durability of the drug. The median overall survival (MOS) was approximately 17 months, compared to 12 months for patients Efficacy of TCR-T in solid tumors We all know that CAR-T is extremely effective in hematologic tumors**, but it is not interesting in solid tumors. So what is the efficacy of TCR-T in solid tumors? Pancreatic cancer Pancreatic cancer (PC) is a malignant tumor that occurs in the pancreas, with a 3-year survival rate of less than 5%, and is known as the "king of all cancers". KRAS mutations are common in tumors, and G12D is the more common mutation in KRAS. The TCR-T cells** provide a new cellular immunity** method for pancreatic cancer patients, and the genetically engineered autologous T cells can clone and express two allogeneic HLA-C restricted TCRs, which can be tried in pancreatic cancer patients with KRAS12D mutations. Typical cases A 71-year-old woman was diagnosed with adenocarcinoma of the pancreatic head at the age of 67 after pancreatitis and biliary stricture reversal, and in 2019, a fine-needle aspiration in an enlarged nodule in the right lower lobe of the lung revealed the presence of lung metastases. In June 2021, the patient received autologous peripheral blood T cells**. On ** day 11 the patient was discharged, absolute neutrophil count was restored at 21 days, and platelets were restored on day 28. At the first clinical follow-up visit 1 month after cell infusion, the patient's metastatic lung lesion regression was observed by computed tomography according to the Response Evaluation Criteria for Solid Tumors (RECIST) 1Version 1, with an overall objective part relief of 62%. At the most recent follow-up at 6 months after cell transplantation, the tumor continued to regress, according to 1Version 1 of RECIST showed an overall partial response rate of 72 percent. The arrows highlight the lesions before and after **. This case shows the efficacy of TCR-T** in pancreatic cancer. Liver cancer The mortality rate of hepatocellular carcinoma (HCC) is on the rise worldwide, but the systemic** effect of advanced HCC is not ideal. In a phase I clinical trial in HBV-positive HCC patients, eight patients received TCR-T cell infusions**. In this trial, one patient had a partial response (PR) that lasted 30 months, while three patients had elevated serum chemokine levels after receiving TCR-T cell transfusions. In the first clinical trial of ADP-A2AFP TCR-T cells in HCC patients, 9 patients received TCR-T cells** and 1 patient achieved complete response (CR) for 6 consecutive months. The results of this trial suggest that targeting AFP TCR-T cells may be another effective strategy for HCC. June 5, 2023 (SCG) presented the latest breakthrough data from its best-in-class autologous HbSAG-specific T cell receptor engineered T cells (TCR-T)**SCG101 at the International Society for Cell and Genomics (ISCT) conference in Paris, France. SCG101 showed significant anti-tumor activity, with a single dose of SCG101 as a single agent** reducing 74 tumors per MRECIST5%。At data cut-off, the duration of tumor response was 69 months. Pre- and post-biopsies showed 100% of HBsag+ hepatocytes in the liver from 557 at baseline96 IU ml dropped to 1 on day 73 IU ML, further reduced to 0 on day 28 after SCG101 infusion08 iu/ml (3.83log decreased). On November 13, 2023, SCG Cell *** SCG) announced the latest clinical data of its first-in-class autologous hepatitis B virus (HBV)-specific T-cell receptor-engineered T cell (TCR-T)**SCG101 at the American Association of Liver Diseases (AASLD) in Boston, USA. Results from a first-in-human clinical trial have shown that SCG101 shows promising antiviral and antitumor activity in patients with advanced HBV-associated hepatocellular carcinoma (HCC). Six patients with advanced HBV hepatocellular carcinoma received TCR+T cell infusion, achieved partial response (PR) in 2 patients, and stable disease (SD) in 2 patients with tumor shrinkage. Tumor response is highly correlated with the antiviral activity of SCG101. As of the data cut-off date, serum HBsAg was reduced in six patients (100%) and four of six patients (67%) achieved a decrease of 1 to 3 Log after SCG101 infusion. HBsAg levels were maintained at 20 IU mL for up to 90 weeks throughout the follow-up period. Tumor shrinkage was observed in all four patients with a decrease in serum HbSag >1 log, and median progression-free survival (PFS) was prolonged in patients with a decrease in HbSag >1 log (25.).8vs 3.1 week). On March 10, 2022, the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China announced that SCG101 autologous T cell injection was successfully approved for clinical trials for the treatment of **hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Conclusion Multiple clinical studies have demonstrated the potential of TCR-T in solid tumors**. So far, TCR-T cell immunity** has achieved good efficacy in solid tumors**, especially for melanoma, synovial sarcoma, and hepatocellular carcinoma**. I hope that immunity can achieve more brilliant results as soon as possible, and I also hope that our domestic anti-cancer drugs can have more people-friendly anti-cancer drugs, so that more cancer patients can benefit. Disclaimer: Kangheyuan Immunity Home is an immunology science popularization platform, the text refers to ** on the Internet, and the copyright belongs to the original author. This article is only for sharing, if it is suspected of infringing your copyright, please contact us to delete, thank you! Resources. 1.late-breaking clinical data at aasld showing scg101 improved tumor reponses and achieved sustained antiviral activates in patients with advanced hbv-related hepatocellular -scg star handset ( 2.scg cell therapy announces late-breaking clinical data at aasld showing scg101 improved tumor reponses and achieved sustained antiviral activates in patients with advanced hbv-related hepatocellular carcinoma | biospace
