Multiple site place-of-care manufactured anti-CD19 CAR T cells safely induce high rates of remission in patients with B-cell malignancies
GAITHERSBURG, Md., Dec. 10, 2021 — Caring Cross, a 501(c)(3) non-profit dedicated to accelerating the development of advanced medicines and enabling access to cures for all patients, everywhere, announced today that Nature Communications has published a scientific manuscript highlighting research demonstrating the effectiveness of place-of-care manufacturing of anti-CD19 CAR T cells for treatment of B-cell malignancies. Place-of-care manufacturing is defined as near the point of patient treatment allowing cell products to be produced and infused without need for cryopreservation.
The manuscript, entitled, “Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients,” reported that novel CD19-targeting CAR-T cells (CAR19-T cells) similarly manufactured using automation at separate sites in Cleveland, USA and Moscow, Russia achieved complete response rates of 73% in adult B-cell Lymphoma (NHL) and 89% in pediatric B-cell Acute Lymphocytic Leukemia (ALL), respectively. For NHL complete responders, the one-year survival rate was 92.9%, with a median duration of response yet to be reached. For ALL complete responders with a median follow-up of 17 months, the one-year survival rate was found to be 79.2% with a median duration of response of 10.2 months. Based on these findings, it was concluded that use of place-of-care manufactured CAR-T cell products results in clinical outcomes that are effective in the treatment of patients with B-cell malignancies.
Dr. Marcos de Lima, Director of Stem Cell Transplantation and Cellular Therapy at The Ohio State University Medical Center, and one of the lead investigators on the clinical trial, commented: “Our studies show that place-of-care manufacture of CAR-T cells results in a consistent cell product and produces effective clinical outcomes, despite being manufactured in two disparate clinical centers located in the US and Russia. We were able to make fresh CAR-T cells in as little as 8 days, which is very important for patients with rapidly progressing disease. We therefore conclude that place-of-care manufacture of CAR-T cells is a valid and valuable model for the manufacture and distribution of CAR-T cells among multiple clinical centers, and particularly important for patients with rapidly progressive, symptomatic lymphoma and ALL.”
In addition to demonstrating that place-of-care manufacture of CAR-T cells results in a consistent cell product and effective clinical outcomes, the research team determined that fresh CAR19-T cells, which can only be manufactured at the place-of-care, reduce tumor burden faster in vivo in NSG mice than cryopreserved CAR19-T cells, immediately reducing the tumor burden, while frozen CAR19-T cells first permitted tumor growth before controlling growth. Moreover, the researchers found that place-of-care manufacture of CAR19-T cells resulted in a highly comparable CAR-T cell product composition between the multiple clinical centers and a low production failure rate, demonstrating the robustness of the manufacturing process.
Dr. Michael Maschan, Director of the Department of Hematopoietic Stem Cell Transplantation at the Dmitriy Rogachev National Center for Pediatric Hematology and Oncology in Moscow, Russia, commented: “Place-of-care manufacturing of CAR-T cells offers several advantages over centralized manufacturing, including reduced vein-to-vein time due to lack of transport to a centralized facility and the ability to infuse fresh and not necessarily cryopreserved products. Simplified logistics increases the flexibility to make decisions based upon patient disease status, for example split-dosing in the instance of high tumor burden. The high response rates we have seen in our clinical trials are outstanding considering that we were able to essentially treat all-comers due to the short manufacturing times of patient-derived CAR-T cell products, which are only possible when they are manufactured at the place-of-care. This has tremendous benefits for patients, particularly those with advance disease that need to be treated as soon as possible. We are delighted with the clinical results to date and look forward to future innovations to further improve patient outcomes.”
Dr. Boro Dropulić, Executive Director of Caring Cross, commented: “This is the first study that definitively demonstrates the feasibility of place-of-care manufacturing of gene-modified cell products between muliple centers. We show that when the same device, materials, reagents and protocols are used to manufacture CAR-T cells, even between two disparate clinical centers, the gene-modified cell products are highly consistent with a low product failure rate. The clinical outcomes for patients were especially remarkable considering that almost all the patients enrolled were treated, even patients that otherwise would not be eligible due to their advanced disease, demonstrating the enormous value of this approach. Place-of-care manufacturing also offers the potential to dramatically reduce the cost of these transformational therapies to a fraction of their current cost due to obviating the need for transportation and the cost of multiple layers of quality and custodial assurance that are required for centralized manufactured CAR-T cell products. The next step will be to expand CAR-T cell clinical trials to include more clinical centers and support the development of regulatory pathways for the approval of CAR-T and other gene-modified cellular products that are manufactured at the place-of-care.”
The full paper may be accessed via the Nature Communications website at http://www.nature.com/ncomms.
About Caring Cross
Caring Cross is a 501(c)(3) non-profit dedicated to accelerating the development of advanced medicines and ensuring access to cures for all patients, everywhere. To enable its mission, Caring Cross is mobilizing a growing community of healthcare professionals, scientists, engineers, community advocates, donors, investors and business leaders to support the development of technologies and candidate medicines and technologies. Currently, Caring Cross is advancing several initiatives that aim to improve the accessibility, affordability and applicability of CAR-T technology and stem cell gene therapy. These opportunities include developing and implementing affordable solutions for the manufacture of CAR-T cells, advancing a decentralized, place-of-care cell manufacturing model and developing its first therapeutic candidate, an anti-HIV duoCAR-T cell therapy designed to suppress HIV replication and eliminate HIV-expressing cells in people with HIV. A stem cell gene therapy for Sickle Cell Disease and Beta-Thalassemia is also in development. For more information on Caring Cross visit https://caringcross.org/.