PHILADELPHIA, PA — Hepatocellular carcinoma (HCC), better known as liver cancer, is a particularly aggressive form of cancer that often leaves healthcare providers grappling for treatment options. This cancer’s stealthy ability to hide from the immune system has posed significant challenges in achieving favorable outcomes. However, a recent clinical trial published in Nature Medicine offers new hope. The trial showcases a novel, personalized neoantigen vaccine therapy that has demonstrated encouraging anti-tumor efficacy. This ground-breaking therapy has shown promise in patients who found no relief from their original front-line treatment for liver cancer. This pivotal research hails from the Vaccine & Immunotherapy Center at The Wistar Institute.
This clinical trial, helmed by Philadelphia biotherapeutics company, Geneos Therapeutics, featured a collaborative team including The Wistar Institute. Their product, a “Personalized neoantigen vaccine“, was tested on patients with advanced hepatocellular carcinoma. The results have provided a new ray of hope in the medical world.
Among the 36 participants enrolled in the trial, 34 were evaluable under the trial guidelines. Out of these, eleven showcased tumor regression as per the clinically defined Response Evaluation Criteria in Solid Tumors (RECIST). This translates to a promising tumor regression rate of 30.6%. Furthermore, eight of these patients had partial vaccine responses, with tumors decreasing in size. In one patient, the tumor reduced enough to open the possibility for surgical removal. Three patients had complete responses with total elimination of observable tumors. Even more encouragingly, nine additional patients exhibited stable disease under the treatment.
As one peers into the gravity of these findings, one cannot help but appreciate the potential implications. These promising results could indicate a significant boost in survival rates for patients grappling with this notoriously aggressive and challenging-to-treat cancer. While Phase 1/2 safety and efficacy studies are merely the first steps in clinical advancement of a new therapeutic, these positive results extend a glimmer of hope for a brighter future for liver cancer patients.
The secret behind this progress lies in the body’s immune system and its “Killer T cells”. These cells are designed to eradicate foreign elements, such as viruses in host cells. However, recognizing tumor antigens hiding within host cells has always been a challenging task. As cancer cells multiply, they can overwhelm the host with rapid cell division. But they also incorporate mutations or “mistakes” in several of the cancer cells’ protein sequences. These mutations result in neoantigens (NeoAg), uniquely expressed in cancers as a by-product of cellular dysfunction.
Scientists from Geneos Therapeutics collaborated with The Wistar Institute Vaccine & Immunotherapy Center to design a unique gene assembly process. This process creates highly consistent and effective NeoAg building blocks, driving effector T cells consistently in vivo.
Their research demonstrated that neoantigens produced by liver cancer don’t typically trigger potent immune responses. However, their improved neoantigen vaccine strings, along with the inclusion of immune-stimulating signals, could potentially train the immune system to better recognize and eradicate the malignancy.
The team’s technology was able to include specific T cell expansion signals associated with the activation of CD4 and CD8 Killer T cell immunity built into the vaccines’ DNA designs. These design elements showed that the technologies were well tolerated and could protect preclinical models from cancer challenge.
David B. Weiner, Ph.D., Executive VP, Vaccine & Immunotherapy Center director at Wistar, expressed his pleasure at the role his institute played in this monumental advancement. He said, “Advancing the next generation of nucleic acid immune weapons for impacting intractable cancers is a major focus of our team.”
While it might be too soon to claim victory over liver cancer, these encouraging results certainly signal a step in the right direction. The medical world watches with great anticipation as this neoantigen vaccine therapy opens up a new avenue in cancer treatment. With further research and clinical trials, we may soon see a significant difference in the way liver cancer is treated and given the severity of this illness, this cannot come soon enough.
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