TPIV > I don't know what to think...they're merging with Marker Therapeutics which has made some pretty bold claims about their MultiTAA T-cells which address limitations of CAR-T and supposedly have similar efficacy as KITE's allogenic CAR-T with longer duration and practically zero SAE's and a much lower cost.
Dr. Leen and her team use T cells with tumor specificity mediated via their native T-cell receptors. These cells are expanded from the patient’s peripheral blood using antigen-presenting cells (specifically, dendritic cells in this case). These cells are loaded with overlapping peptide libraries that span up to five tumor-expressed antigens, which selectively enriches for tumor-specific populations, she explained.
“As such, the cells are not genetically engineered, and since the T-cell products target multiple tumor-expressed antigens simultaneously, the risk of immune escape due to antigen loss is minimized,” she said.
The tumor-expressed antigens in the product were MAGE-A4, PRAME, survivin, NYESO1, and SSX2. They are also known as shared, or cancer/testis, antigens, which are protein antigens whose normal expression is restricted to adult testicular germ cells but which are aberrantly activated and expressed in various types of cancer.
Clinical Trial in Lymphoma
Their first-in-human study included 27 patients with Hodgkin lymphoma (n = 10), aggressive non-Hodgkin lymphoma (n = 15), or composite lymphoma (n = 2). Of these patients, 12 had active disease and 15 received the product after autologous or syngeneic stem cell transplant (without lymphodepletion), for which the infusion was considered adjuvant therapy. Three dose levels were evaluated, the lowest being 10 million cells. Patients received 2 infusions, 2 weeks apart. No adverse events were observed after infusion at any dose level, Dr. Leen reported.
The active disease group included a number of patient types, including patients in second or subsequent relapse; in first relapse for indolent lymphoma after first-line therapy for relapse; in first relapse if immunosuppressive chemotherapy was contraindicated; with primary refractory or persistent disease after first-line therapy; with multiple relapses but now in remission and with a high risk for relapse; and with lymphoma as a second or transformed malignancy.
“After we infused our cells, we saw that strong activity of the T cells was generated against the five target antigens in patient blood samples. And remarkably, we didn’t just see an increase in signal against the antigens we were targeting, but also against other nontargeted, tumor-expressed antigens indicating in vivo epitope spreading, which further amplified the benefit of our therapy,” Dr. Leen reported.
T-cell activity correlated with clinical benefit, in almost all of these heavily pretreated patients. Out of 12 patients with active disease, 5 had complete responses. Of these, 3 responses were ongoing for more than 2 years and 1 has persisted for more than 1 year. One complete responder died of pneumonia after 4 months in remission.
Three patients achieved stable disease, with one patient remaining stable for 1 year. Three patients had progressive disease as the best response, and several patients were yet to be assessed.
Among the 15 patients receiving infusions as adjuvant therapy, who were heavily pretreated prior to transplant, all 15 remain in remission at a median of 17 months after infusion.
Dr. Leen commented, “In the setting of lymphoma, we showed it’s feasible to generate T cells. They have proven safe, and we have seen evidence of tumor lysis, in vivo epitope spreading, and clinical benefit.”
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
