autologous T cell cancer therapeutics / Gilead, Amgen - LARVOL DELTA

Combination of AMG 160, a PSMA x CD3 half-life extended bispecific T-cell engager (HLE BiTE) immune therapy, with an anti-PD-1 antibody in prostate cancer (PCa). (ASCO-GU 2020) - P1; "Activation of autologous T cells within the tumor slices was assayed by flow cytometry, and secretion of cytokines into culture supernatants was measured by Meso Scale Discovery (MSD). Together these data suggest that antitumor efficacy of the AMG 160 HLE BiTE immune therapy can be increased by co-treatment with anti-PD-1. These data provide a rationale for evaluating this combination in future clinical studies. Research Funding: Amgen Inc."

IO Biomarker • PD-L1

Combination of AMG 160, a PSMA x CD3 half-life extended bispecific T-cell engager (HLE BiTE) immune therapy, with an anti-PD-1 antibody in prostate cancer (PCa). (ASCO-GU 2020) - P1; "Activation of autologous T cells within the tumor slices was assayed by flow cytometry, and secretion of cytokines into culture supernatants was measured by Meso Scale Discovery (MSD). Together these data suggest that antitumor efficacy of the AMG 160 HLE BiTE immune therapy can be increased by co-treatment with anti-PD-1. These data provide a rationale for evaluating this combination in future clinical studies. Research Funding: Amgen Inc."

IO Biomarker • PD-L1

Regression of epithelial cancers in humans following t-cell receptor gene therapy targeting human papillomavirus-16 E7. (ASCO 2018) - "...Patients received a single infusion of autologous T cells that were gene-engineered to express an HLA-A*02:01-restricted T-cell receptor that targets HPV-16 E7 (E7 T cells)...E7 T cell infusion was followed by high-dose systemic aldesleukin... Tumor regression can occur following treatment of an epithelial cancer with gene-engineered T cells. These findings support continued study of E7 T cells and possibly other types of gene-engineered T cells in epithelial cancers."

Anal Carcinoma • Gynecologic Cancers • Renal Cell Carcinoma

Phase 1 study of AMG119, a chimeric antigen receptor (CAR) T cell therapy targeting DLL3, in patients with relapsed/refractory small cell lung cancer (SCLC). (ASCO 2019) - P1; "AMG 119 is an adoptive cellular therapy that consists of a patient’s autologous T cells that have been genetically modified ex vivo to express a transmembrane CAR that targets DLL3 and redirects cytotoxic T cell specificity to DLL3-positive cells. The dose expansion phase will seek to confirm the MTCD or RP2CD and obtain further safety and efficacy data. Clinical trial information: NCT03392064"

Clinical • P1 data

Influence of Cytoreductive and Immunmodulatory Drugs on Bispecific T-Cell Engager-Based Approaches in AML (ISAL 2017) - "Previously, we demonstrated that the CD33/CD3 BiTE® antibody construct AMG 330 is able to recruit residual autologous T cells, resulting in effective cytotoxicity against primary AML cells...Clinical experience in ALL has shown a clear correlation of leukemic burden and a cytokine release syndrome (CRS) during treatment with blinatumomab...Furthermore antibody mediated unwanted toxicity is treated with steroids (dexamethasone, DEX) or tocilizumab (TOC, IL-6R antibody)...Therefore we evaluated the influence of cytoreductive- (azacytidine, AZA; decitabine, DEC) and immunmodulatory drugs (DEX, TOC) on antibody-mediated T-cell function...Importantly, exposure to DEX led to a significantly reduced T-cell responsiveness. For management of severe CRS, TOC could be considered as a targeted biologic therapy that preserves BiTE®-dependent T cell function._x000D_"

Bispecific • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Leukemia • Oncology

Selectivity and specificity of engineered T cells expressing KITE-585, a chimeric antigen receptor targeting B-cell maturation antigen (BCMA) (AACR 2017) - "One such technique is to use adoptive transfer of engineered autologous T cells expressing a chimeric antigen receptor (CAR) directed against a tumor antigen. These studies highlight the tractability of this cell microarray approach for determining the specificity of novel CAR constructs expressed in T cell. Demonstrating the selectivity and specificity of anti-BMCA CAR T cells further supports the progression of KITE-585 towards Phase 1 clinical studies in MM patients."

CAR T-Cell Therapy • Biosimilar • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Development of KITE-585: A fully human BCMA CAR T-cell therapy for the treatment of multiple myeloma (AACR 2017) - "One such approach is to use adoptive transfer of engineered autologous T cells expressing a chimeric antigen receptor (CAR) directed against malignant cells. The results of these studies highlight the potential of targeting BCMA with adoptive transfer of engineered T cells for the treatment of MM. Given these positive findings, progress towards Phase 1 clinical studies in MM patients with KITE-585 is continuing."

CAR T-Cell Therapy • Biosimilar • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Blinatumomab-Induced T Cell Activation at Single Cell Transcriptome Resolution (ASH 2019) - "Blinatumomab connects patients’ autologous T cells and target cells to form immunologic synapse which potently triggers the activation signaling cascades in T cells and guides T cells to recognize and induce perforin/granzyme-mediated lysis of CD19+ B-ALL cells. Furthermore, T cell co-regulatory receptors were identified as potential targets accountable for blinatumomab sensitivity or resistance mechanisms. The study demonstrated that the collected cellular transcriptional profiles can serve as resource to explore novel strategies to enhance the efficacy of blinatumomab."

IO Biomarker • CCL2 • CCL3 • CCL4 • CD8 • CXCL10 • FASLG • IFNG • IL2RA • LDHA • NFKBIA • PGAM1 • PRF1

Nonclinical safety assessment of AMG 553, an investigational anti-FLT3 CAR-T therapy. (ASCO 2019) - "AMG 553 is a novel, investigational, adoptive cellular immunotherapy for the treatment of relapsed refractory AML, consisting of autologous T cells genetically modified ex vivo to express a transmembrane chimeric antigen receptor (CAR) to target FLT3 protein on the surface of AML cells irrespective of FLT3 mutational status. The nonclinical safety data support AMG 553 as a novel therapeutic to target FLT3 protein on AML cells irrespective of FLT3 mutational status, while only affecting a percentage of normal hematopoietic stem and progenitor cells."

Clinical • IO Biomarker

"Hope for great results. Also look to TCR @KitePharma, autologous T cell transfer #iova and t-cell activation @CueBiopharma for t-cell work on solid tumors." (@DrVerret)