Engineered IL-7 synergizes with IL-12 immunotherapy to prevent T cell exhaustion and promote memory without exacerbating toxicity

Cancer immunotherapy is moving toward combination regimens with agents of complementary mechanisms of action to achieve more frequent and robust efficacy. However, compared with single-agent therapies, combination immunotherapies are associated with increased overall toxicity because the very same mechanisms also work in concert to enhance systemic inflammation and promote off-tumor toxicity. Therefore, rational design of combination regimens that achieve improved antitumor control without exacerbated toxicity is a main objective in combination immunotherapy. Here, we show that the combination of engineered, tumor matrix-binding interleukin-7 (IL-7) and IL-12 achieves remarkable anticancer effects by activating complementary pathways without inducing any additive immunotoxicity. Mechanistically, engineered IL-12 provided effector properties to T cells, while IL-7 prevented their exhaustion and boosted memory formation as assessed by tumor rechallenge experiments. The dual combination also rendered checkpoint inhibitor (CPI)–resistant genetically engineered melanoma model responsive to CPI. Thus, our approach provides a framework of evaluation of rationally designed combinations in immuno-oncology and yields a promising therapy

Using Genograms as a Methodology For Understanding Family Dynamics

Genograms are an important tool used by clinicians and therapists working with families, however; the use of genograms in research has not reached its full potential. In this working paper, we propose a methodology for using genograms as a research instrument. We propose a three step process which includes: 1) qualitative coding of transcripts, 2) superimposing of concepts on genograms, and 3) genogram comparison across families. Following this method of analysis, genograms can be used to identify common dynamics across families and illustrate how various family interactions lead to a variety of phenomena such as Elder Family Financial Exploitation (EFFE)