Cancer Immunology, Immunotherapy
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including ‘‘position papers,’’ general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology. Tumor immunologists, clinical oncologists, virologists, and medical microbiologists involved in the development of methods of treatment and therapies for cancer patients will benefit from the information contained in this journal. Cancer Immunology, Immunotherapy is the official journal of the Association for Cancer Immunotherapy.

Immunotherapy: Combinations that work
Targeted cancer therapies can modulate host immune responses, which raises the possibility that efficacy might be improved by combining these therapies with immune-stimulating agents. Preclinical data in support of such a strategy have been reported in two recent papers.

Knowing that the activity of the monoclonal antibody trastuzumab (which targets ERBB2) in breast cancer is partly due to antibody-dependent cellular cytotoxicity (ADCC), which depends on natural killer (NK) cells, Ronald Levy and colleagues investigated whether activation of the co-stimulatory molecule CD137 (also known as TNFRSF9 and 4-1BB) in NK cells could improve trastuzumab efficacy. In vitro studies showed that co-incubation of ERBB2-expressing breast cancer cell lines and purified human NK cells with trastuzumab upregulated CD137 on the NK cells. These activated NK cells were able to kill trastuzumab-coated ERBB2-expressing breast cancer cell lines through ADCC, and this was enhanced by a CD137 agonistic antibody. To investigate this combination in vivo, the authors used a xenograft model of human breast cancer cells in athymic mice, which lack functional T cells but which have NK cells. Mice were injected with trastuzumab on day 3 after tumour inoculation, and the CD137 antibody was injected on day 2, day 3 or day 4. Trastuzumab followed by CD137 antibody treatment significantly reduced tumour growth and increased mouse survival compared with either antibody alone. Interestingly, if ERBB2-expressing and non-expressing cell lines were transplanted into opposite flanks on the same mouse, the combination treatment only had an enhanced effect against the ERBB2-expressing tumour, indicating specificity for trastuzumab-bound cells, which may translate to reduced systemic toxicity. Treatment with trastuzumab followed by the CD137 antibody was also effective against a xenograft of a primary ERBB2-expressing human breast tumour in severe combined immunodeficient (SCID) mice (which have NK cells but which lack a functional adaptive immune response). Finally, the authors examined circulating NK cells in patients with breast cancer who were receiving trastuzumab therapy and, although heterogeneous, overall there was an approximately twofold induction in CD137 expression in the NK cells following trastuzumab infusion. These data suggest that the timing of antibody administration should be carefully considered in any clinical studies of this combination.