Program: Oral and Poster Abstracts
Session: 624. Lymphoma: Therapy with Biologic Agents, excluding Pre-Clinical Models: Novel Immunotherapy Strategies in Lymphoma
To date 28 clinical-grade multiTAA-specific T cell lines have been generated comprising CD3+ T cells (mean 94±2%) with a mixture of CD4+ (mean 46±7%) and CD8+ (mean 46±6%) T cells, which expressed central and effector memory markers (CD45RO+/CD62L+/CCR7+ -- mean 22±5%; CD45RO+/CD62L+/CCR7- -- 12±4%; CD45RO+/CD62L-/CCR7- -- 35±6%) (n=28). The expanded lines recognized the targeted antigens PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin (range 1-354, 0-496, 0-330, 0-379 and 0-304 spot forming units (SFU)/2x105 input cells, respectively in IFNg ELIspot, n=28). None of the lines reacted against non-malignant autologous recipient cells (3±3.7% specific lysis; E:T 20:1).
We have treated 18 patients to date: 9 with HL, 8 with aggressive NHL (diffuse large B-cell, mantle cell, or peripheral T cell lymphomas), and 1 with a composite lymphoma. Patients have received 0.5-2x107 multiTAA-T cells/m2 without adverse events. Of 11 patients who were infused as adjuvant therapy all but 1 remain in remission (range 1-24 months post-infusion). Seven patients have received multiTAA-specific T cells to treat active disease. Of these, 1 had transient disease stabilization followed by disease progression, 3 have stable disease 3-6 months post-multiTAA-specific T cells while the remaining 3 (all with HL) have all had complete responses, as assessed by PET imaging. These clinical responses correlated with the detection of tumor-reactive T cells in patient peripheral blood post-infusion directed against both targeted antigens as well as non-targeted TAAs including MAGEA2B and MAGE C1, indicating antigen/epitope spreading. Thus, infusion of autologous multiTAA-targeted T cells directed to PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin has been safe and provided clinical benefit to patients with lymphomas.
Disclosures: Off Label Use: Tumor-specific T cells administered under an investigator-initiated IND. Brenner: Celgene: Other: Collaborative Research Agreement ; Bluebird Bio: Equity Ownership , Membership on an entity’s Board of Directors or advisory committees ; Cell Medica: Other: Licensing Agreement . Heslop: Celgene: Other: Collaborative research agreement ; Cell Medica: Other: Licensing Agreement . Rooney: Celgene: Other: Collaborative research agreement ; Cell Medica: Other: Licensing Agreement .
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