Healthcare (Commonwealth Union) – A recent study from UCLA showcases a novel approach to screening T cells, integral components of the body’s immune system, for attributes crucial to the efficacy of cell-based therapies. This method involves sorting T cells based on their surface receptor proteins, which facilitate their binding to specific threats, as well as the type and quantity of molecules they release to initiate cell death or immune responses.
Through this screening technique, researchers identified three previously unknown T-cell receptors naturally targeting prostate cancer. Validation experiments revealed that T-cell receptors associated with higher secretion levels were more likely to provoke a response against cancerous cells. The functional rate of T-cell receptors using this method was approximately ten times higher compared to previous techniques.
In the complex universe of the human immune system, T-cells stand as stalwart defenders, tirelessly patrolling the body to identify and neutralize threats. At the heart of their remarkable capabilities lie T-cell receptors intricate molecular structures that serve as the eyes and ears of the immune system. These receptors play a pivotal role in distinguishing between healthy cells and invaders, orchestrating targeted immune responses essential for maintaining health and combating disease.
The structure of TCRs is highly specialized, comprising two distinct chains – alpha (α) and beta (β) chains in the case of most TCRs, although there are also gamma (γ) and delta (δ) chains found in a smaller subset of T-cells. Each chain consists of constant and variable regions, with the latter being particularly important for antigen recognition. The variable regions contain hypervariable loops, often referred to as complementarity-determining regions (CDRs), which directly interact with antigens, enabling T-cells to discern between self and non-self-molecules.
Researchers of the study indicated that immunotherapy, which harnesses the body’s natural defense mechanisms, remains a rapidly expanding area of study in the treatment of cancer and other serious diseases. Engineered T cell-based immunotherapies hold promise due to their ability to precisely target disease markers recognized by genetically modified receptors. Since 2017, seven immune cell-based therapies have received approval from the Food and Drug Administration for the treatment of various blood and skin cancers.
The researchers utilized nanovials, minute hydrogel containers with bowl-like structures developed at UCLA. These containers were engineered to contain specialized molecules, tailored to capture individual cells along with specific secretions. Partillion Bioscience, a company co-founded and led by some of the researchers, commercially provides these nanovials.
In their initial assessment, the team examined a pool of 20 million T cells obtained from a single healthy donor’s blood sample. Various sets of nanovials were designed with targets corresponding to distinct common viruses. This investigation affirmed the capability of nanovials to identify T cells and their receptors responsive to viruses.
Subsequently, a second experiment varied out with a different patient addressed a more complex challenge: targeting rare prostate cancer markers previously identified by the scientists. These molecular targets not only facilitated the capture of T cells but also induced them to release specific molecules that eradicate target cells. Furthermore, in additional trials, the nanovials were equipped with molecules enabling them to capture multiple types of immune-activating secretions.
Researchers of the study indicated that the discovery of three novel receptors for prostate cancer in this study holds promising implications for the development of innovative immunotherapies against tumors. The demonstrated capacity to identify T cells that not only attach to disease-specific targets but also release ample molecules provoking an immune reaction is anticipated to offer significant advantages in uncovering further disease-targeting receptors, advancing cellular therapies, and implementing these therapies for patient benefit. Employing conventional laboratory methods to label and analyze the nanovials and their contents expands accessibility, enabling more researchers to adopt this novel technique.
The researchers also made a disclosure stating that Joseph de Rutte is employed by Partillion Bioscience, a company advancing nanovial technology commercially. De Rutte, Dino Di Carlo, and the University of California hold financial interests in Partillion Bioscience. Owen Witte maintains consulting, equity, and/or board affiliations with Trethera Corporation, Kronos Biosciences, Sofie Biosciences, Breakthrough Properties, Vida Ventures, Nammi Therapeutics, Two River, Iconovir, Appia BioSciences, Neogene Therapeutics, 76Bio, and Allogene Therapeutics. Some authors are also inventors on patent applications that belong to the University of California. The deeper knowledge of the immune systems response to cancer and pathogens is key to the develop of therapies.
