Effective Targeting of Multiple B-Cell Maturation Antigen-Expressing Hematological Malignances by Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T Cells.

B-cell maturation antigen (BCMA) expression has been proposed as a marker for the identification of malignant plasma cells in patients with multiple myeloma (MM). Nearly all MM tumor cells express BCMA, while normal tissue expression is restricted to plasma cells and a subset of mature B cells. Consistent BCMA expression was confirmed on MM biopsies (29/29 BCMA+), and it was further demonstrated that BCMA is expressed in a substantial number of lymphoma samples, as well as primary chronic lymphocytic leukemia B cells.

Akt1 and -2 inhibition diminishes terminal differentiation and enhances central memory CD8 T-cell proliferation and survival.

The CD8 T-cell response comprises terminally differentiated effector cells and antigen-experienced memory T cells. The latter encompass central (T) and effector (T) memory cells. T cells are superior in their protection against viral and bacterial challenges and mediation of antitumor immunity due to their higher proliferative ability upon antigen re-encounter.

Selective inhibition of regulatory T cells by targeting the PI3K-Akt pathway.

Despite the strides that immunotherapy has made in mediating tumor regression, the clinical effects are often transient, and therefore more durable responses are still needed. The temporary nature of the therapy-induced immune response can be attributed to tumor immune evasion mechanisms, mainly the effect of suppressive immune cells and, in particular, regulatory T cells (Treg). Although the depletion of Tregs has been shown to be effective in enhancing immune responses, selective depletion of these suppressive cells without affecting other immune cells has not been very successful, and new agents are sought.

Tumor-specific CD4+ melanoma tumor-infiltrating lymphocytes.

Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) can mediate objective and durable tumor regressions in patients with metastatic melanoma. CD8+ tumor-reactive TIL are well studied in humans and animals, yet the function of tumor-infiltrating CD4+ T lymphocytes in patient treatments remains controversial. We recently demonstrated that CD4+ TILs are not necessary for objective responses in patients.

Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement.

Treatment of patients with adoptive T-cell therapy requires expansion of unique tumor-infiltrating lymphocyte (TIL) cultures from single-cell suspensions processed from melanoma biopsies. Strategies which increase the expansion and reliability of TIL generation from tumor digests are necessary to improve access to TIL therapy. Previous studies have evaluated artificial antigen presenting cells for their antigen-specific and costimulatory properties.

The promising future of proteomics in cancer diagnosis and treatment.

Cancer is a leading cause of death in developed countries. For most cancers, a patient's prognosis improves dramatically when the disease is detected at an early stage. Although advancements in imaging technology have dramatically improved early detection, many cancers go undetected until it is too late.