The hottest Immunotherapy Substack posts right now

Two main cure strategies are emerging: a "hard reset" with engineered immune cells (CAR‑T/CAR‑NK) that deplete disease‑causing B cells and is moving toward off‑the‑shelf, in‑body delivery for one‑shot remissions.
A "soft reset" uses inverse or tolerogenic vaccines and Treg/dendritic‑cell approaches to retrain the immune system to tolerate self‑antigens instead of attacking them.
Advances in cancer immunotherapy (CAR‑T, checkpoint modulation, in‑vivo delivery, gene editing) are accelerating autoimmune cures, but challenges remain with cost, safety (e.g., cytokine release, neurotoxicity, vector risks) and equitable access.

Alzheimer's will likely need a combination of therapies instead of a single 'magic bullet' drug.
Recent results—modest GLP‑1 signals, negative phase 3 trials, and limited amyloid drug benefits—suggest single agents aren't enough and that the timing of interventions matters.
Immune strategies such as an Alzheimer's vaccine could be an important component of a multi-pronged treatment plan when used at the right disease stage.

Clinical trials should be treated as active engines of discovery, not just a final yes/no test; faster, more frequent trials create feedback loops that turn clinical data into better drug designs.
The CAR‑T story shows that small, information‑rich human studies can reveal why early designs fail and guide specific fixes that lead to major breakthroughs.
Regulatory, manufacturing, and institutional barriers make these learning‑focused trials slow and costly, so policy and technical changes are needed to lower barriers, enable adaptive development, and collect richer in‑human measurements.

The study of Michigan and Nebraskan families led to the discovery of mutated mismatch repair genes causing hereditary colorectal cancers like Lynch syndrome.
Mismatch repair genes play a crucial role in maintaining DNA integrity and preventing cancer development. Defects in these genes can lead to conditions like microsatellite instability.
Individuals with Lynch syndrome have higher cancer risks associated with certain genes like MLH1 and MSH2, but a relatively good clinical outcome is observed with improved survival rates.

The immune system has key components like T cells which play a crucial role in fighting cancer by harnessing latent immunity.
Researchers like James Allison and Tasuku Honjo have made significant contributions in understanding how cancer evades the immune system and how immune checkpoints like CTLA-4 and PD-1 can be targeted to enhance immune response against cancer.
Cellular immunotherapy, particularly immune checkpoint inhibitors targeting PD-(L)1, has shown great potential in treating various cancers, with some patients showing long-term remissions and ongoing innovative developments in this field.

Get a weekly roundup of the best Substack posts, by hacker news affinity:

Metastatic cancer is often very serious and many people diagnosed don't survive long. However, some treatments are making progress in helping patients achieve long-term remission.
New treatments, especially immunotherapies, are showing promise in making metastatic cancer disappear in some patients. This is a big deal because it used to be very rare.
There's still a lot of potential to improve cancer treatments. Researchers are exploring many different strategies, and exciting possibilities are on the horizon to help more patients.

An innovative Fc engineering approach can adjust antibody-dependent cytokine release without impacting cell-killing functions. This shows that manipulating cytokine release independently is possible.
Different IgG isotypes have varying abilities to stimulate proinflammatory cytokine release. This indicates the importance of isotype selection beyond just cytotoxicity.
Engineering antibodies to selectively engage FcγRs can potentially enhance immune responses. This opens up new possibilities for optimizing antibody immunotherapies against cancer.

Cancer cells have various tricks to evade targeted therapies like changing their driver mutation and cell identity, stealing the mitochondria from T cells, and spreading predominantly during sleep.
Immune response strategies like immune checkpoint inhibitors, therapeutic cancer vaccines, antibody-drug conjugates, and oncolytic viruses are being developed to combat cancer.
Combining different immunotherapy strategies and approaches like engineering T cells show promise in overcoming the challenges of treating cancer and improving patient outcomes.