Immuno-oncology breakthroughs: from precision medicine to modulating the tumor microenvironment

The European Association for Cancer Research (EACR) explores the most exciting cancer research from Europe and globally. Clarivate Life Sciences Editor Joan Tur reviews the top three trends from their recent immuno-oncology event, and their implications for the future of cancer treatment.

Despite pandemic-driven clinical trial delays across multiple therapy areas, novel immuno-oncology approaches continue to advance at a steady pace (see Figure 1), showing promise to support the many unmet needs of cancer patients.

The use of precision medicine, the modulation of the tumor microenvironment and the discovery of potential new actionable targets were amongst the topics covered in the third “EACR – Defence is the Best Attack” conference, which was held as a virtual worldwide event in February.

Here are some of the highlights tracked by the Clarivate immuno-oncology experts at the conference, which provide fascinating insight into the dynamic field of cancer immunotherapy.

 

Figure 1. Immuno-oncology therapies advance at a steady pace

Source: Cortellis Competitive Intelligence

 

DNA in the cerebrospinal fluid as a biomarker to evaluate responses to brain cancer

Brain tumors are a prominent exception to the overall robust efficacy of cancer immunotherapy, with only a small fraction of patients responding to checkpoint inhibition. Data obtained from the tumor microenviroment can be used in precision medicine approaches to select the most beneficial treatments and improve patient outcomes. However, due to its location, obtaining representative biopsies from brain tumors is a highly invasive and challenging surgical procedure.

Joan Seoane (VHIO and Mosaic Biomedicals) presented a safer and less-invasive approach using the circulating tumor DNA (ctDNA) found in the cerebrospinal fluid as a liquid biopsy. ctDNA is shed from cells in the tumor, including immune cells in its microenvironment, and then released to the CSF where it can be detected. This approach provides fundamental information about the immune cell landscape, allowing it to make predictions about the potential benefit of immunotherapies, to evaluate patient responses to treatments in real time and to discover potential new targets for drug development.

Myc inhibitors to prevent tumor immune evasion

Sílvia Casacuberta-Serra from Peptomyc presented preclinical data from Omomyc (OMO-103), a cell-penetrating peptide therapeutic that inhibits the oncoprotein Myc, which is deregulated in a wide range of cancers and often associated with highly aggressive tumors.

Myc has been known for a long time as a potential target for anti-cancer therapy, with its inhibition resulting in decreased proliferation and enhanced apoptosis of tumor cells. These new preclinical data showed for the first time that Myc inhibition using Omomyc also interferes with the mechanisms of tumor immune evasion. The therapy reduced tumor burden and increased recruitment and activation of immune cells to the tumor site in a mouse model of non-small cell-lung cancer (NSCLC), the second most common cancer in both men and women. Similar data were observed regardless the driving mutations of the cancer, confirming that the immuno-stimulatory effect is not dependent on the mutational profile of the tumor.

 

Eosinophils as potential targets to treat breast cancer metastasis

In the majority of cases, breast cancer mortality is the result of tumor metastasis. Sharon Grisaru (Tel Aviv University) focused her presentation on eosinophils, a type of immune cell normally associated with allergic reactions. Recent evidence suggests that these cells are also involved in anti-cancer responses, as hinted by the fact that eosinophils are present in almost 95% of lung cancer metastases from breast cancer patients.

Using a mouse model of breast cancer-derived lung metastasis, the researchers showed that eosinophils are actively recruited to the metastases via a CCR3-independent pathway. They demonstrated their importance in anti-cancer responses, showing an increase in the tumor burden when these cells were depleted.

However, these anti-cancer responses are not performed directly by the eosinophils themselves: eosinophils are first activated by a series of factors in the tumor microenvironment (including IFN-gamma and TNF-alpha), which makes them start secreting CXCL9/10. Cytotoxic CD8+ T cells are then attracted by these signals, and are the ones that directly attack the tumor cells. Altogether these data open the door to a variety of potential new therapies targeting eosinophils in cancer.

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