Shooting for the Moon: Better Assays to Hit Our Cancer Research Targets

3239CA02_1AIn his address to the clinicians, researchers, and patients at the American Association for Cancer Research meeting in April, US Vice President Joe Biden, revealed that the goal of the #cancermoonshot initiative is to accomplish 10 years of cancer research in just five years, effectively doubling the pace of cancer research (1).

Treatments developed from cancer research have come a long way with dramatic differences in the experiences and prognoses for patients, just looking back over the last 25 years. How can we double the pace of cancer research? The #cancermoonshot will one, encourage data sharing among researchers, particularly data from clinical trials. Second, it seeks to increase collaboration across industry, academic and government scientists—each community being positioned to make unique contributions to the field. And third, the initiative looks to change the current grants award process that encourages scientists to keep data and results “quiet” until they can be published or protected legally as intellectual property.

Immunotherapy is an especially hot field in cancer research (2) that relies on the immune system to better fight cancer. Our understanding of the immune system and the way tumors evade being destroyed is evolving every day. Just within the last two years, several PD-1- and PD-L1-blocking antibodies received “breakthrough designation” for melanoma, Hodgkin’s lymphoma, and non-small cell lung cancer because of their promising preliminary results. Some of these immunotherapy biologics have already gained US FDA approval. Even more encouraging are preliminary reports from combination immunotherapy treatment, where biologics drugs are used in tandem to engage molecules of two pathways at the same time. For instance, combinations of PD1 and CTLA4 inhibitors may be particularly effective at achieving an antitumor effect (2) and Genentech has shown that co-blockade of TIGIT and PDL1 is promising (2).

A factor that has slowed the pace of research before in the development of immune checkpoint and other immunotherapy antibodies is the lack of reliable, low variability bioassays to characterize the function of the biologic drug. Researchers were mostly limited to assays using primary cells isolated from donor blood to assess the activity of a biologic against a target molecule in immunotherapy. However, these assays are highly variable due to the inherent donor-to-donor variation from the differences in genetic background and the immune status of the blood donors. The assays that use primary cells are difficult to implement and difficult to transfer from lab to lab because of the skill required for successful primary cell culture and performing the assays—not every technician has the same touch, and assay precision suffers.

Schematic illustrating the principle of the TIGIT/PD-1 combination bioassay.
Schematic illustrating the principle of the TIGIT/PD-1 combination bioassay.

Promega is uniquely positioned with the scientific and technical expertise in assay development to create sensitive yet easy-to-use assays based on proven technologies such as bioluminescent chemistries and reporter assays. Indeed Promega has created a suite of reporter-based bioassays to measure Fc Effector or Immune Checkpoint mechanism of action with high precision and accuracy, thereby obviating the problems associated with primary cell-based assays. Chief among these assays is a combination immunotherapy bioassay designed to assess the activity of biologics that engage both the PD-1/PD-L1 and TIGIT/CD155 pathways simultaneously. A GEN Tutorial from May 1 issue introduces such a bioassay pair and highlights the advantages of this approach in the research and development of biologics that target these important pathways, providing researchers an important tool to help speed the pace of discovery.

Literature Cited

  1. Transcript of Vice President Joe Biden’s Address to American Association of Cancer Researchers 2016 [Internet Accessed: May, 10, 2016]
  2. Mahoney, K.M., Rennert, P.D. and Freeman, G.J. (2015) Combination cancer immunotherapy and new immunomodulatory targets. Rev. Drug Disc. 14, 561–84.
  3. Cheng, Z-J. et al. (2016) Bioassays power combination immunotherapy. Genetic Engineering and Biotechnology News 36: 9. [Internet: Accessed: May 10, 2016]
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Michele Arduengo

Michele Arduengo

Supervisor, Digital Marketing Program Group at Promega Corporation
Michele earned her B.A. in biology at Wesleyan College in Macon, GA, and her PhD through the BCDB Program at Emory University in Atlanta, GA where she studied cell differentiation in the model system C. elegans. She taught on the faculty of Morningside University in Sioux City, IA, and continues to mentor science writers and teachers through volunteer activities. Michele supervises the digital marketing program group at Promega, leads the social media program and manages Promega Connections blog.

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