{"id":339,"date":"2024-08-24T07:02:33","date_gmt":"2024-08-24T07:02:33","guid":{"rendered":"https:\/\/mrna.creative-biolabs.com\/blog\/?p=339"},"modified":"2024-08-24T07:02:33","modified_gmt":"2024-08-24T07:02:33","slug":"cd-mrna-vaccines-for-sustained-anti-tumor-immune-response","status":"publish","type":"post","link":"https:\/\/mrna.creative-biolabs.com\/blog\/cd-mrna-vaccines-for-sustained-anti-tumor-immune-response\/","title":{"rendered":"CD: mRNA Vaccines for Sustained Anti-tumor Immune Response"},"content":{"rendered":"

mRNA-4157 (V940) is a personalized tumor mRNA vaccine<\/a><\/strong><\/span>. By utilizing lipid nanoencapsulation technology, mRNA-4157 can deliver up to 34 tumor-specific antigens (also called tumor neoantigens) that are specifically tailored for\u00a0tumor patients\u00a0into the body, ultimately stimulating the\u00a0immune\u00a0system to produce specific immune cells, thereby achieving the purpose of controlling and treating tumors.<\/span><\/p>\n

There are currently many studies on mRNA-4157, including the famous KEYNOTE-942 study and KEYNOTE-603 study.<\/span><\/p>\n

At this year’s American Society of Clinical Oncology (\u00a0ASCO\u00a0) annual meeting, the latest follow-up data of KEYNOTE-942 were announced. The results showed that the combination of mRNA-4157 and the PD-1 inhibitor pembrolizumab can reduce the risk of surgical resection in patients with high-risk tumors. Patients with\u00a0melanoma\u00a0(stage III\/IV) have a 49% lower risk of recurrence or death, and a 62% lower risk of distant metastasis or death. This result also confirms the potential of mRNA-4157 in treating cancer.<\/span><\/p>\n

Recently, some of the research results from the KEYNOTE-603 study were also published on Cancer Discovery<\/em>. This study mainly evaluates the safety, tolerability, and immunogenicity of mRNA-4157 alone or in combination with pembrolizumab in patients with different solid tumors.<\/span><\/p>\n

The results showed that in 4 patients with surgically resected non-small cell\u00a0lung cancer\u00a0(1 mg mRNA-4157 monotherapy) and 12 patients with surgically resected stage II-IV\u00a0melanoma\u00a0(1 mg mRNA-4157 + 200 mg pembrolizumab treatment), mRNA-4157 demonstrated a good safety profile, with no patients experiencing grade 4\/5 adverse events or dose-limiting toxicities. Most adverse reactions were grade 1\u20132, with the most common being\u00a0pyrexia, fatigue, and injection site pain, overall tolerable.<\/span><\/p>\n

In terms of immunogenicity, mRNA-4157 can effectively induce and enhance specific T cell responses against tumor neoantigens. More importantly, these responses persisted 30 weeks after treatment, which also proves that mRNA-4157 has long-term anti-tumor ability.<\/span><\/p>\n

KEYNOTE-603 is a Phase 1 multi-center, open-label clinical trial. According to different tumor types, the study is divided into five AE parts. This article mainly announces the safety of Part A non-small\u00a0cell carcinoma\u00a0patients and Part D melanoma patients. safety and immunogenicity data.<\/span><\/p>\n

Four patients with surgically resected non-small cell carcinoma received 1 mg of mRNA-4157 monotherapy every 3 weeks for a maximum of 9 cycles; 12 patients with melanoma received 1 mg of mRNA-4157 in combination with 200 mg of paclitaxel every 3 weeks. For brolizumab treatment, the combined treatment time is up to 9 cycles. Patients can then continue treatment with pembrolizumab monotherapy at the same dose for up to 18 cycles (approximately 1 year). Baseline data for all patients are shown in the table below.<\/span><\/p>\n

In the end, 12 patients completed the study, 2 patients were lost to follow-up, 1 patient terminated the study due to adverse events unrelated to mRNA-4157 treatment, and 1 patient died of unknown causes one year after completing treatment.<\/span><\/p>\n

Regarding the safety of patients who received at least one dose of mRNA-4157, whether treated with mRNA-4157 alone or in combination with pembrolizumab, all patients experienced at least one treatment-related 1\/2 grade adverse event, of which the most common events were fever (n = 7, 63.6%), fatigue (n = 6, 54.5%), and injection site pain (n = 5, 45.5%), but most events were between 3 and 4 resolved within days without causing treatment delay or interruption.<\/span><\/p>\n

Overall, no grade 4\/5 treatment-related adverse events were observed, and no dose-limiting toxicities were observed. This also shows that mRNA-4157 is safe and generally tolerable.<\/span><\/p>\n

In terms of immunogenicity, analysis of peripheral blood mononuclear cells from treated patients showed that patients who received mRNA-4157 monotherapy developed specific CD4 and CD8 T cell responses against tumor neoantigens after treatment. , whereas almost no such reactions were observed before treatment.<\/span><\/p>\n

Such responses were also observed in patients in the combination treatment group. This shows that mRNA-4157 can successfully activate T cells in patients to produce an immune response against tumor neoantigens.<\/span><\/p>\n

The study also found that these T cell responses were durable and could still be detected even 100 days after the last dose. This shows that not only does mRNA-4157 stimulate strong immune responses, but these responses are maintained for a long time.<\/span><\/p>\n

In conclusion, the results of this trial show that mRNA-4157 is well tolerated and can effectively induce specific CD4 and CD8 T cell responses to tumor neoantigens, whether as a monotherapy or in combination with pembrolizumab. This reaction can last for a long time. This result also supports the Food and Drug Administration’s breakthrough therapy designation for the combination of mRNA-4157 and pembrolizumab.<\/span><\/p>\n

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