Targeting IDH2R140Q and other neoantigens in acute myeloid leukemia.

For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality. Furthermore, ∼60% of patients will ultimately relapse after allo-HSCT, thus, underscoring the need for novel therapeutic strategies that are safe and effective.

Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing.

T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease.

Beyond CD19 CAR-T cells in lymphoma.

Adoptive transfer of CD19-specific chimeric antigen receptor T-cells (CAR-T cells) has transformed the treatment paradigm of relapsed/refractory (R/R) CD19 B-cell malignancies, dramatically improving remission rates and cures in patients with chemo-refractory disease. However, the applicability of CD19 CAR-T cells is limited to B cell malignancies and antigen loss can result in treatment failure, prompting the exploration of alternative targets to overcome tumor escape via CD19 antigen loss, as well as extend the CAR-T cell platform to treat Hodgkin and T cell lymphomas. This review highlights recent clinical trials testing CAR-T cell targets beyond CD19.

Virus-specific T cells for malignancies - then, now and where to?

Purpose Of Review: Virus-associated malignancies are a global health burden, constituting 10-12% of cancers worldwide. As these tumors express foreign viral antigens that can elicit specific T cell responses, virus-directed immunotherapies are a promising treatment strategy. Specifically, adoptive cell transfer of virus-specific T cells (VSTs) has demonstrated the potential to eradicate cancers associated with certain viruses.

Evaluation of cyclin A1-specific T cells as a potential treatment for acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for relapsed or refractory acute myeloid leukemia (AML). However, more than half ultimately experience disease relapse that is associated with a dismal median survival of just 6 months, highlighting the need for novel therapies. In the current study we explore the therapeutic potential of targeting cyclin A1 (CCNA1), a cancer-testis antigen that is overexpressed in malignant blasts and leukemic stem cells.

Adoptive Immunotherapy with Antigen-Specific T Cells Expressing a Native TCR.

Although T cells genetically modified with chimeric antigen receptors became the first immune effector product to obtain FDA approval, T-cell products that recognize their antigenic targets through their native receptors have also produced encouraging responses. For instance, T cells recognizing immunogenic viral antigens are effective when infused in immunosuppressed patients. A large number of tumor antigens are also expressed on nonviral tumors, but these antigens are less immunogenic.

Analysis of common cytogenetic abnormalities in New Zealand pediatric ALL shows ethnically diverse carriage of ETV6-RUNX1, without a corresponding difference in survival.

Background: The frequency of common cytogenetic abnormalities in pediatric acute lymphoblastic leukemia (ALL) is known to vary by geographic location and ethnic origin. This study aimed to determine the frequency of hypodiploidy, ETV6-RUNX1, BCR-ABL1, and MLL rearrangement within New Zealand's pediatric ALL population and to assess whether the frequency of these ALL prognostic markers varies according to ethnicity.

Procedure: The New Zealand Children's Cancer Registry provided information for all registered pediatric ALL patients that were diagnosed between 2000 and 2009, with medical records available for 246 patients.

Illness perceptions in patients with gout and the relationship with progression of musculoskeletal disability.

Objective: Illness perceptions are key determinants of behavior directed at managing disease. Although suboptimal disease management has been reported in patients with gout, patients' perceptions of illness have not been systematically studied. The aim of this study was to examine illness perceptions in patients with gout.