Immunotherapy

Notes

• T-cells are an important type of killer white blood cell. They specialize in hunting down and killing cancer cells or cells infected by viruses. That sounds great! But you can imagine situations where if your T-cells are too active, they might start to hurt, rather than help - for example, lots of autoimmunity is caused by T-cells that misrecognize normal cells as cells that need to be killed; also, think about when you get the flu - your temperature starts to rise, if it got too high it could kill you.

  • So the immune system evolved a series of breaks (or checkpoint proteins) to help keep T-cells in check. If these checkpoint proteins become engaged, T-cells 'turn-off' and become less likely to attack a target cell.

  • In cancer, several things happen:

    1. T-cells naturally get turned-off. A cell can only kill so many tumor cells before it becomes exhausted.

    2. Cancer cells sometimes evolve the ability to trick the T-cells into turning themselves off.

  • So what these researchers discovered was some of the key proteins involved in turning the T-cells off (CTLA4 and PD1). More excitingly, they showed that inhibiting these proteins made the T-cells less likely to be turned-off, and enabled them to more effectively kill cancer cells.

  • The first immunotherapy drug in this class inhibited late-stage, aggressive CTLA4 - in melanoma it raised survival from close to zero to about 10-15%.

  • The next major innovation was anti-PD1 drugs. These drugs are racking up impressive clinical results so fast, it is hard to quantify just how good they are.

  • What does this mean for someone with HER2+ breast cancer?:

    • Immunotherapy has made less inroads into breast cancer, so far. It seems to work best on cancers with high mutation rates (lung cancer from smoking, melanoma from sun exposure etc.). But people are working hard to find ways to bring immunotherapy to the field - for example using antibodies that directly point the T-cells at the tumor cells.

Links

• Why Cancer Immunotherapy - Breathtaking new hope that can help end cancer for good.

• Immunotherapy: How the Immune System Fights Cancer (2018)

• Developing Cancer Immunotherapy – James P. Allison (2018)

• Jim Allison, Ph.D., Nobel Prize News Conference (2018)

• Accelerating Immunotherapy target discovery using immune repertoire sequencing (2018)

• B-T.cr forum - Community discussion site about immune repertoire analysis.

• B-T.CR Wiki Home

• Genetically modified T-cells hunting down and killing cancer cells. Represents one of the next major frontiers in clinical oncology (2019)

• Beyond Checkpoint Blockade for Cancer Immunotherapy (2018)

• Enpicom - Platform for personalizing immunotherapies.

• Parker Institute - Brings together the field’s top scientists & clinicians to accelerate the development of breakthrough immunotherapies to turn cancer into a curable disease.

• [Type 1-programmed dendritic cells drive antigen-specific latency reversal and immune elimination of persistent HIV-1 (2019)](https://www.ebiomedicine.com/article/S2352-3964(19)30222-1/fulltext)

• Athelas - Neutrophils, Lymphocytes, Platelets, WBCs, Morphology, and Cell Activation all within minutes from a fingerprick of blood.

• "Building a Unified Cancer Immunotherapy Data Library" by Lacey Kitch and Ben Kamphaus (2019)

• Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1 (2020) (HN) (Reddit)

• Projecting single-cell transcriptomics data onto a reference T cell atlas to interpret immune responses (2020)

• The Antibody Society - International non-profit supporting antibody-related research and development.