Clinical Impact of Somatic Genomic Testing on Breast Cancer Care.

Developments in our understanding of the molecular biology of breast cancer have had a direct impact on the investigations needed to provide optimal breast cancer care. Somatic genomic tests are now used routinely to inform decisions regarding adjuvant chemotherapy use in selected early breast cancer patients, and to identify patients with advanced disease who can potentially benefit from novel targeted agents. In this overview, we describe the somatic genomic tests currently available within the National Health Service (NHS) for early and advanced breast cancer patients.

Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function.

The costimulatory receptor 4-1BB is expressed on activated immune cells, including activated T cells. Antibodies targeting 4-1BB enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T cell-dependent anti-tumor immunity in pre-clinical cancer models. We found that T regulatory (Treg) cells infiltrating human or murine tumors expressed high amounts of 4-1BB.

Risk- and response-adapted strategies for the management of Hodgkin lymphoma.

Therapy for Hodgkin lymphoma (HL) is associated with excellent long-term survival rates, of 80% of more. Extended follow up has described late treatment-related toxicities, principally secondary malignancies, cardiovascular disease and infertility. Given the young age of many patients, there is a desire to offer a more personalised approach, correlated to individual tumour biology that enables treatment de-escalation in low risk patients to reduce toxicity, and treatment intensification in high risk patients to reduce treatment failure.

The Use of Anti-CD40 mAb in Cancer.

Immunomodulatory monoclonal antibody (mAb) therapy is at the forefront of developing cancer therapeutics with numerous targeted agents proving highly effective in selective patients at stimulating protective host immunity, capable of eradicating established tumours and leading to long-term disease-free states. The cell surface marker CD40 is expressed on a range of immune cells and transformed cells in malignant states whose signalling plays a critical role in modulating adaptive immune responses. Anti-CD40 mAb therapy acts via multiple mechanisms to stimulate anti-tumour immunity across a broad range of lymphoid and solid malignancies.

Mogamulizumab and the treatment of CCR4-positive T-cell lymphomas.

Glyco-engineering has been developed to enhance the pharmacological properties of monoclonal antibodies (mAbs) resulting in superior immune effector function. Mogamulizumab is the first approved glyco-engineered therapeutic antibody and first approved mAb to target the CC chemokine receptor 4 (CCR4). CCR4 is principally expressed on Tregs and helper T cells (Th) where it functions to induce homing of these leukocytes to sites of inflammation.