Abstract 6750: Validation of a platform to develop new dendritic cell vaccines for cancer immunotherapy

Abstract

Abstract Osteosarcoma is the most common malignant form of bone cancer that generally causes patients to die of pulmonary metastasis. If detected before the tumor has metastasized, osteosarcoma has a 75% survival at 5 years after the conventional therapy with surgery and chemotherapy. However, most osteosarcomas are high-grade tumors that grow quickly and spread before being detected, lowering patient survival to 20%. Our unique protocol using the human platelet lysate PLTMax® allows establishing tumor cell lines without genetically modifying cells and with minimal genetic drift. The use of PLTMax® and allogeneic tumor cell cultures has proven to be a major advantage for the generation of large amounts of rich tumor antigen libraries for dendritic cell (DC) vaccines. This protocol was used in an autologous dendritic cell/allogeneic tumor lysate vaccine developed at the Mayo Clinic and licensed to Mill Creek Life Sciences (MCLS) to treat newly diagnosed glioblastoma (GBM), which normally has a poor survival rate at only 2%. The technology was used in a phase I clinical trial (MC1272) performed at the Mayo Clinic. The clinical outcomes proved over a 10 time increase in survival rate of patients that received the DC vaccine after the conventional therapy, providing over 20% three-year survival rate. Our technology differs from other clinically used DC vaccines in three primary ways: a) Highly efficient cell line establishment: The unique method for generating tumor cell lines uses Mill Creek Life Sciences’ PLTMax®, a media supplement derived from human platelets. PLTMax® more closely mimics the native microenvironment of tumors and is used to reduce genetic drift and senescence. b) High genetic fidelity: GBM tumor cells expanded via PLTMax® maintain genetic fidelity and TAA expression—a feat that has not been previously achieved by any other GBM cell culture method. c) Reduction of treatment delays and inclusion of all patients that qualify for treatment: Because we will use allogeneic tumor cell lines, we will be able to avoid delays in treatment caused by the time required to culture autologous tumor cell lines, and all patients may receive treatment without exclusion. Through our preliminary work we transferred the technology from a labor-intensive, small-scale approach, to an automated scalable system. Our ultimate goal is to apply this strategy to not only osteosarcoma, but also several other tumor types to validate it as a platform. Like osteosarcoma, there are other therapy-refractory cancers that we believe can benefit from the use of our platform technology, through the use of DC vaccines that offer an immune response against a wider panel of tumor antigens. Citation Format: Vanesa Alonso-Camino, William Mirsch. Validation of a platform to develop new dendritic cell vaccines for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6750.