Lifeboat Foundation

Understanding how major histocompatibility complex class (MHC) molecules and peptides interact within the immune system is crucial for the advancement of biological sciences and medicine. A better understanding of how and when the immune system is activated can lead to treatments in diseases such as cancer or for the development of new vaccines.

MHC-peptide exchange technology attempts to replicate the immune response where peptide exchange occurs on an MHC molecule. The combination of the peptide sequence and the MHC molecule define the strength of the binding affinity resulting in a weak or strong interaction. In order for in vivo T cell epitope to be immunogenic, it must be able to bind a compatible MHC molecule and remain bound for long enough to be presented to and recognized by T cells to elicit an immune response. This shows that a strong binding affinity of MHC/peptide sequence in vitro may indicate potential strong immune interactions of antigen specific T cells in the desired model test sample. Ultimately obtaining this crucial peptide-MHC partnership, where binding affinity is the optimal amount, and the subsequent T cell reaction is sufficient for a therapeutic response, is difficult and cumbersome. There are many different technologies to explore MHC-peptide binding.

Chimeric antigen receptor (CAR) therapies involve the use of engineered receptors capable of redirecting immune cells to recognize and destroy cancer cells expressing a specific antigen. Currently, CAR-T cells, T cells equipped with CAR, dominate the field of CAR therapy. Since 2017, over 700 clinical trials involving CAR-T therapy have been registered and the U.S. Food and Drug Administration (FDA) has approved six CAR-T therapies for the treatment of leukemia, lymphomas, and multiple myeloma (Fig. 1) ^[1]. However, despite its clinical significance, several factors contribute to the limitations of CAR-T therapy. First, as collecting T cells is costly and time-consuming, this may not be feasible for patients already suffering from a compromised immune system. Second, CAR-T therapies mainly focus on treating hematological malignancies, having limited effectiveness in treating solid tumors. Third, CAR-T cells struggle to penetrate the tumor microenvironment (TME), which can hinder their therapeutic function. To overcome these limitations, promising CAR designs have emerged for multi-target CAR-T alongside novel therapies that utilize other immune cell types such as CAR-Natural killer (NK) and CAR-Macrophage (M) cells.

Figure 1. Timeline of CAR-T FDA approvals in the US. B-ALL, B cell acute lymphoblastic leukemia; LBCL, large B cell lymphoma; MCL, mantle cell lymphoma; MM, multiple myeloma; R/R, relapsed/refractorySource: adapted from Maakaron, J, et al. 2022^[1].

Beware, bad guys—your DNA is in the air.

Summary: ChatGPT has successfully passed a radiology board-style exam, demonstrating the potential of large language models in medical contexts. The study utilized 150 multiple-choice questions mimicking the style and difficulty of the Canadian Royal College and American Board of Radiology exams.

ChatGPT, based on the GPT-3.5 model, answered 69% of questions correctly, just under the passing grade of 70%. However, an updated version, GPT-4, managed to exceed the passing threshold with a score of 81%, showcasing significant improvements, particularly in higher-order thinking questions.

Summary: A new study discovered not all microglia are the same, challenging existing beliefs. A unique subset of these cells, the ARG1+microglia, important for proper cognitive functions, were identified in mice, with evidence suggesting a similar subset exists in humans.

Microglia lacking the protein ARG1 led to less exploratory behavior in mice, indicating cognitive deficits. These discoveries open exciting new possibilities for understanding brain diseases and developing novel therapies.

The discovery of a new type of stem cell in deer antlers could lead to breakthroughs in human regeneration.

NewLimit, a company working towards the radical extension of human healthspan using epigenetic reprogramming has announced it has secured $40 million in Series A funding from prominent investors including Dimension, Founders Fund, and Kleiner Perkins.

This investment further bolsters the company’s belief that therapies to delay, halt or even reverse aging can be found through the exploration of epigenetic reprogramming. With a strong belief that their innovative approach can also address various age-related diseases, NewLimit aims to revolutionize the field of aging biology and pave the way for transformative advancements in healthcare.

Longevity. Technology: Epigenetic reprogramming is an emerging but exciting field of geroscience. It involves the identification of specific sets of transcription factors that can induce changes in gene expression and cellular behavior, effectively reversing or modifying the epigenetic markers associated with aging. This approach offers a unique opportunity to rejuvenate cells and tissues, potentially slowing down or even reversing the effects of aging and its related diseases. NewLimit says that while its products are designed to treat aging itself, the company also believes “these products could treat or prevent many diseases associated with aging, including fibrosis, infectious disease, and neurodegenerative disease.”

A new publication in the May issue of Nature Aging by researchers from Integrated Biosciences, a biotechnology company combining synthetic biology and machine learning to target aging, demonstrates the power of artificial intelligence (AI) to discover novel senolytic compounds, a class of small molecules under intense study for their ability to suppress age-related processes such as fibrosis, inflammation and cancer.

The paper, “Discovering small-molecule senolytics with deep neural networks,” authored in collaboration with researchers from the Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, describes the AI-guided screening of more than 800,000 compounds to reveal three drug candidates with comparable efficacy and superior medicinal chemistry properties than those of senolytics currently under investigation.

“This research result is a significant milestone for both longevity research and the application of artificial intelligence to drug discovery,” said Felix Wong, Ph.D., co-founder of Integrated Biosciences and first author of the publication. “These data demonstrate that we can explore chemical space in silico and emerge with multiple candidate anti-aging compounds that are more likely to succeed in the clinic, compared to even the most promising examples of their kind being studied today.”

Dr. Steven Gazal, an assistant professor of population and public health sciences at the Keck School of Medicine of USC, is on a mission to answer a perplexing question: Why, despite millions of years of evolution, do humans still suffer from diseases?

As part of an international research team, Gazal has made a groundbreaking discovery. They’ve become the first to accurately pinpoint specific base pairs in the human genome that have remained unaltered throughout millions of years of mammalian evolution. These base pairs play a significant role in human disease. Their findings were published in a special Zoonomia edition of the journal Science.

Gazal and his team analyzed the genomes of 240 mammals, including humans, zooming in with unprecedented resolution to compare DNA.