505 A novel anti-PD-L1/anti-VEGF bispecific VHH antibody exhibits a synergistic anti-tumor effect compared to the monospecific VHH antibodies

Background Clinical research has demonstrated that combining immunotherapy anti-PD-1/PD-L1 antibodies with anti-angiogenic VEGF/VEGFR blockers improves cancer treatment outcomes. These combined therapies have received approval for several cancer types. A bispecific antibody targeting both PD-L1 and VEGF could enrich the antibody concentration in tumor tissue by specifically binding to PD-L1 expressed in the tumor, thereby increasing… Continue reading 505 A novel anti-PD-L1/anti-VEGF bispecific VHH antibody exhibits a synergistic anti-tumor effect compared to the monospecific VHH antibodies

445 Analysis and feasibility of cerebrospinal fluid (CSF) lymphocyte expansion from patients with melanoma leptomeningeal disease (M-LMD)

Background Leptomeningeal disease (LMD), the spread of tumor cells to the subarachnoid space and CSF, is a devastating, fatal complication of metastatic cancers. LMD has a dismal prognosis with patients living 4–8 weeks after diagnosis. The incidence of LMD has been increasing with improved patient survival with advances in immunocellular and targeted therapies as well… Continue reading 445 Analysis and feasibility of cerebrospinal fluid (CSF) lymphocyte expansion from patients with melanoma leptomeningeal disease (M-LMD)

503 In silico design of AR148, a TGF-{beta} SelecTrapTM for selective binding to TGF-{beta}1 and TGF-{beta}3 to reduce toxicities and widen the therapeutic window

Background TGF-β (Transforming Growth Factor-beta) plays a significant role in cancer progression and has immunosuppressive effects within the tumor microenvironment (TME), inhibiting the function of T cells and thereby suppressing their anti-tumor response. Blocking or inhibiting TGF-β signaling may alleviate this immunosuppression and create a more favorable environment for T cell infiltration. However, pan-inhibition of… Continue reading 503 In silico design of AR148, a TGF-{beta} SelecTrapTM for selective binding to TGF-{beta}1 and TGF-{beta}3 to reduce toxicities and widen the therapeutic window

427 Cancer neutrophil encyclopedia: a deep dive into antigen-presenting warriors

Background Neutrophils, the most efficient defenders against pathogens, are essential for tumor microenvironment balance and homeostasis.1–3 However, given their plasticity and short half-life which made them too fragile to be profiled, it poses complex challenges regarding how neutrophils are imprinted and adapt specific fates across cancers.4–7 Methods Here we designed a one-two-punch sorting strategy, generated… Continue reading 427 Cancer neutrophil encyclopedia: a deep dive into antigen-presenting warriors

423 Effective targeting of osteosarcoma by ex vivo expanded TCR {gamma}{delta} T cells

Background Osteosarcoma is the primary malignant bone tumor with peak incidence in both children and young adults. Despite significant progress in treatment, individuals with metastatic or recurrent disease have poor prognosis due to lung metastasis with limited clinical trials. While autologous chimeric antigen receptor (CAR) therapies have shown promise, they face limitations due to their… Continue reading 423 Effective targeting of osteosarcoma by ex vivo expanded TCR {gamma}{delta} T cells

320 Quantitative clinical pharmacology and mechanistic modeling of TAK-102, a GPC3 targeted CAR-T therapy armored with IL-7 and CCL19, in a phase-1 clinical trial in solid tumor patients

Background TAK-102 is an investigational GPC3 targeted CAR-T therapy armoured with IL-7 and CCL19 to enhance proliferation/persistence and induce host-immune cell infiltration respectively. An open-label, non-randomized phase-1 study (NCT04405778) was conducted in patients with GPC3+ solid tumors to evaluate safety and tolerability of TAK-102 as well as identifying recommended Phase-2 dose (RP2D) level. Methods As… Continue reading 320 Quantitative clinical pharmacology and mechanistic modeling of TAK-102, a GPC3 targeted CAR-T therapy armored with IL-7 and CCL19, in a phase-1 clinical trial in solid tumor patients

365 Artificial intelligence-based dynamic single-cell imaging reveals enhanced migration and immune synapse formation by IDP-023, an allogeneic g-NK cell product

Background Fc&x025B;R1-deficient Natural Killer (g-NK) cells are a naturally occurring subset of NK cells that occur in a portion of individuals latently infected with cytomegalovirus. The lack of Fc&x025B;R1-adapter protein results in exclusive signaling through CD3 and consequently, significantly enhanced CD16-mediated antibody-dependent cellular cytotoxicity (ADCC) compared to conventional NK (cNK) cells in bulk coculture assays… Continue reading 365 Artificial intelligence-based dynamic single-cell imaging reveals enhanced migration and immune synapse formation by IDP-023, an allogeneic g-NK cell product

329 Pre-clinical efficacy of a novel anti-GPC3 in vivo CAR-M for hepatocellular carcinoma

Background Chimeric antigen receptor macrophage (CAR-M) cell therapies have the potential to mediate robust anti-tumor immunity via phagocytosis, cytokine/chemokine release, antigen presentation, activation of the tumor microenvironment (TME) and T cell recruitment. Phase I data have demonstrated that autologous ex vivo CAR-M are well-tolerated, induce reprogramming of the solid TME, promote epitope spreading, and mediate… Continue reading 329 Pre-clinical efficacy of a novel anti-GPC3 in vivo CAR-M for hepatocellular carcinoma

197 Serum interleukin-2 levels in the first 24-72 hours post CD19 CAR T cell infusion is a robust biomarker of CAR T cell expansion in leukemia and lymphoma patients treated with Axi-cel or Brexu-cel

Background A key contributing factor to clinical activity in CD19 CAR T cell therapy is CAR expansion.1-3 However, measuring CAR T cells early in the first days after therapy can be challenging in the clinic. Many studies have detected CAR T cells within the first week of therapy, but flow cytometry and genetic detection of… Continue reading 197 Serum interleukin-2 levels in the first 24-72 hours post CD19 CAR T cell infusion is a robust biomarker of CAR T cell expansion in leukemia and lymphoma patients treated with Axi-cel or Brexu-cel

246 A GPRC5D and BCMA bispecific CAR-T product demonstrated dual antigen targeting capability and efficacy against multiple myeloma cells bearing BCMA mutations associated with treatment resistance

Background Although B-cell Maturation Antigen (BCMA)-targeting immunotherapies greatly improve survival in multiple myeloma (MM) patients, antigen escape remains a significant challenge preventing long-term tumor control.1 2. Post-BCMA treatment and relapsed patients often exhibit mutations, biallelic loss, and downregulation of BCMA gene expression.3 We previously reported the development of a G Protein-Coupled Receptor Class C Group… Continue reading 246 A GPRC5D and BCMA bispecific CAR-T product demonstrated dual antigen targeting capability and efficacy against multiple myeloma cells bearing BCMA mutations associated with treatment resistance