autoimmunity

Season 4, Episode 3: Peering Inside the Immune Response for Novel Antibodies with Nima Emami

Episode Contributors: Seth Bannon, Michael Chavez, Nima Emami

Episode Summary: Antibodies are one of the greatest tools we have in our therapeutic arsenal and have transformed the way we treat cancer and autoimmunity. But we still largely develop these drugs using guess and check methods, massively slowing down the process. However, our own B cells are constantly making new antibodies against the pathogens and diseases we routinely suffer from, creating a gold mine of drugs floating around inside all of us. We just need to find them! Recognizing this challenge, Nima and his team at Avail Bio have leveraged their deep experience in computation and systems immunology to build a platform that massively screens the antibody repertoire of patients who have successfully cleared a disease. With it, they find ready-to-deploy antibody drugs that could treat everything from cancer to autoimmunity and even reprogram our own immune system!

About the Guest

  • Nima Emami is the CEO & co-founder of Avail Bio. He received a PhD in Bioinformatics from the UCSF Cancer Center, and studied Bioengineering, Electrical Engineering and Computer Science at UC Berkeley.

Key Takeaways

  • The immune system contains a massive diversity of antibodies that hold clues on how to fight disease. Avail has developed a platform to discover and develop these antibodies for cancer and autoimmune disease.

  • Companies that spin out of universities can pair with accelerators early on to both raise funding and make progress with a small amount of capital. The most challenging part of pulling IP out of a university is speed. Public universities that generate many spinouts are often overwhelmed with the amount of inventions disclosed concurrently, which lengthens the time required for tech transfer.

  • Avail’s platform combines synbio, machine learning and genomics to both discover and validate targets, and ultimately translate those targets into drugs. Failure of clinical stage programs in cancer trials can be traced back to the failure of mouse models to faithfully recapitulate the cancer biology or the immunobiology that we see in humans.

  • The future that Avail hopes to create is one where drugs developed using their platform will reach patients, thereby changing the drug discovery paradigm to be more data-driven.

Impact

  • The platform that Avail is building peers inside the human immune response to find and develop novel antibodies to cure cancer and autoimmune disease.

Company: Avail Bio

Season 2, Episode 5: What Regulates the Regulatory T cells? with Jessica Cortez

First Author: Jessica Cortez

Episode Summary: Whether it's Multiple Sclerosis, Type 1 Diabetes, Lupus, or Crohn's Disease, autoimmunity is a rapidly growing problem that traditional pharmaceuticals have failed to completely cure. While these diseases have very different symptoms, they all have the same root cause -- the body’s immune system is attacking its own healthy organs. Lurking within ourselves are a group of T cells called regulatory T cells that have the power to suppress immune function. These cells have huge potential to be engineered and utilized as a platform to cure any autoimmune disease. Unfortunately, they easily lose their suppressive abilities and can even exacerbate autoimmunity if handled incorrectly. Looking to stabilize regulatory T cells, Jessica and her colleagues perform a CRISPR screen to map which genes are responsible for maintaining their suppressive function. Using this data, Jessica takes the first step to bring this incredibly powerful cell type to the clinic to help millions of patients suffering from a myriad of diseases.

About the Author

  • Jessica performed this work in the lab of Professor Alex Marson at the University of California, San Francisco. The Marson lab is renowned for their work in building and applying synthetic biology tools to understand and improve the therapeutic value of immune cells.

  • Jessica is driven to understand and cure autoimmune diseases because her mother, her sister, and her have all been diagnosed with autoimmune diseases.

Key Takeaways

  • Regulatory T cells can suppress immune reactions, making them an attractive therapeutic to be used to cure any autoimmune disease.

  • These regulatory T cells do not easily maintain their suppressive function, necessitating some engineering to make sure they maintain their therapeutic value.

  • With CRISPR, Jessica turned every gene off one-by-one in regulatory T cells to find which genes were involved in maintaining its suppressive function.

  • Jessica found a gene, USP22, that when expressed, inhibited regulatory T cell function making it a useful target for both autoimmunity and cancer.

Translation

  • While Jessica focused on one of the hits from the screen, there were many more that have massive potential as drug targets or as engineering steps for T cell therapies against autoimmunity.

  • Maintaining a stable regulatory T cell is the vital first step to creating a world where all autoimmune diseases are cured using cells.

Paper: CRISPR screen in regulatory T cells reveals modulators of Foxp3