Category Archives: active immunotherapy

Mutational burden biomarker – not just mismatch repair deficiency

We have discussed mutational burden previously on this blog – in essence, the concept is that tumors with more mutations are more visible to the immune system because the generation of new novel antigenic epitopes allows for adaptive immune responses even when previous adaptive antigen-specific immune responses have been blunted by PD-1 expression. Continue reading

Adenosine – a critical checkpoint in the tumor microenvironment

The tumor microenvironment (TME) includes a host of cells (mesenchymal, immune, vascular), cytokines, and other signaling molecules that serve to abrogate the innate and adaptive immune responses against the tumor. This is appropriate to maintain tissue homeostasis, and to prevent autoimmunity after the rogue cancer cells have been eliminated. Cancer cells co-opt many of these pathways to terminate the effective immune response so that they are not wiped out, rather, proliferate, invade, metastasize and kill, Continue reading

SEMA4D/CD100, a novel target for immune-oncology

Semaphorins are secreted, transmembrane, and glycosylphosphatidylinisotol-anchored glycoproteins that are important in cell to cell signaling. Humans have 20 semaphorins, the most of any species analyzed to date. Their role was originally identified in the development of the nervous system and axonal guidance. Since then, they have been shown to be important in the development and functioning of many tissues including: Continue reading

The levels of immune cells within ovarian cancer tumors correlate with survival

Researches with the Ovarian Tumor Tissue Analyses Consortium analyzed the CD8+ (cytotoxic T-cell) content of tumors from 5,500 patients and compared them with clinical outcome. The analysis was large enough to allow for comparison by histologic subtype – endometrioid, clear cell, mucinous, and low-grade serous ovarian cancer, as well as high-grade serous ovarian cancer. Included in the sample were 3,200 high grade serous ovarian cancers. Continue reading

Early discontinuation of checkpoint inhibition due to immune-related side effects does not have a significant impact on treatment efficacy

A course of treatment with checkpoint inhibitors Yervoy (ipilimumab) and Opdivo (nivolumab) for patients with unresectable or metastatic melanoma is every 3 weeks for a total of four doses. Almost forty percent of patients receiving this combined regimen discontinue treatment because of  immune-related adverse events. Continue reading

Priming cancer for immunotherapy

Augmenting the responses to checkpoint inhibitors, which remove the “breaks” from the immune response, is a very popular area of research. The general concept is to turn immunologically cold tumors hot. For example, triple negative breast cancer (TNBC) is considered an immunologically cold tumor – anti-PD(L)1 therapy has shown responses of just 5-10%. Continue reading

Sitravatinib plus nivolumab in NSCLC

Sitravatinib (MGCD516) is an oral multi-tyrosine kinase inhibitor being developed by Mirati Therapeutics. Last week, the company announced that three of eleven patients with non-small cell lung cancer (NSCLC) with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL who were resistant to checkpoint [anti PD-(L)1 therapy] had confirmed partial responses; because of this, dosing in the 34-patient expansion cohort will proceed. Continue reading

Opdivo and Yervoy, the new front-line standard for poor/intermediate-risk renal cell carcinoma

The results of CheckMate 214 demonstrated that combination checkpoint immunotherapy with nivolumab (Opdivo; anti-PD-1 monoclonal antibody) and ipilimumab (Yervoy; anti-CTLA-4 monoclonal antibody), is superior to sunitinib (Sutent; multikinase inhibitor) in the treatment of patients with newly diagnosed renal cell carcinoma (RCC). Interestingly, prior to sunitinib, another immunotherapeutic approach – interferon-alpha (IFN-α) – was the front-line treatment of choice for renal cell carcinoma, which, like melanoma, is very immune-responsive. Continue reading

New Link’s Indoximod + Keytruda looks promising in Phase 2 advanced melanoma

Indoximod + Keytruda looks promising in Phase 2 advanced melanoma

IDO (indoleamine-2,3-dioxygenase) is an intracellular enzyme found in antigen presenting cells that mediates immune suppression in the tumor microenvironment. Continue reading

Sellas merges with Galena to advance WT1 peptide cancer vaccine

Sellas reversed merged into Galena, a peptide vaccine company whose lead product, NeuVax, for breast cancer failed. Sellas’ lead product is galinpepimut-S for AML (acute myelogenous leukemia) and mesothelioma, as well as other cancers. Continue reading