Ep. 35: CART Therapies Featuring Dr. Maria Themeli
Jan 6, 2015
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Dr. Maria Themeli, a postdoctoral fellow at Memorial Sloan Kettering Cancer Center, shares her groundbreaking research on CAR T-cell therapies, where stem cells are transformed into cancer-hunting assassins. The conversation dives into the complexities and challenges of enhancing T-cell precision in targeting tumors. They also explore intriguing connections between cancer, random mutations, and the immune system's role, along with the impact of methamphetamine use on health. Insights into funding hurdles for early-career researchers add a personal touch to the scientific discussion.
CAR T-cell therapy represents a revolutionary method in cancer treatment, harnessing engineered T-cells to specifically target and destroy tumor cells.
The podcast highlights the crucial role of mentorship and personal experiences in shaping the careers of early-career scientists navigating postdoctoral challenges.
Research into induced pluripotent stem cells aims to address the limited supply of T-cells for CAR therapy, enhancing its effectiveness and sustainability.
Deep dives
Introduction to CAR T-Cell Therapy
Chimeric Antigen Receptor T-cell (CAR T-cell) therapy is emerging as a groundbreaking approach in cancer treatment. This innovative therapy leverages the body’s immune system to target and eliminate tumor cells by engineering T-cells to express receptors that can recognize specific antigens on these cells. The development of CAR T-cell therapy has gained traction, with numerous biotech companies now focused on harnessing this technology. The conversation highlights the excitement surrounding its potential to revolutionize immunotherapy.
The Importance of Personal Experience in Research
The podcast emphasizes the impact of personal experiences on scientific research careers, particularly in the context of postdoctoral training. Researchers often face challenges, such as securing funding and being able to explore ambitious projects, which can lead to setbacks in their careers. The discussion brings attention to the importance of mentorship and support in fostering scientific exploration and innovation, particularly for early-career researchers. Personal anecdotes highlight the struggles and triumphs faced during the transition to independence in the research field.
The Role of Stem Cells in Advancing CAR Therapy
The utilization of induced pluripotent stem cells (iPS cells) in CAR T-cell therapy is highlighted as a promising avenue for research. iPS cells offer the potential for generating an unlimited supply of T-cells, which can be specifically engineered to target tumors. However, challenges remain in achieving optimal differentiation rates and ensuring that the resulting T-cells retain the desired functional characteristics. The ongoing work in this area aims to leverage stem cell technology to create more effective and sustainable cancer treatments.
Concerns Over Off-Target Effects
Off-target effects in CAR T-cell therapy represent a significant concern regarding the safety and efficacy of cancer treatments. Researchers discuss the challenges of ensuring that engineered T-cells only target tumor cells, without affecting healthy tissues that may express similar antigens. Strategies to mitigate these risks include the development of combinatorial antigen approaches and inhibitory chimeric antigen receptors, both designed to enhance specificity. The importance of addressing these concerns is critical for advancing CAR T-cell therapies into widespread clinical use.
The Need for Reform in the Postdoctoral Landscape
The podcast addresses the systemic issues within the postdoctoral training environment, particularly the perception of postdocs as transitional roles rather than as legitimate careers. This stigma can lead to a lack of support and recognition for the vital contributions that postdocs make to the scientific community. Calls for reform emphasize creating sustainable career paths and improving compensation for researchers at this stage. Advocates urge for a reevaluation of the postdoctoral structure to better support the next generation of scientists.
Guest:
From the lab of Michel Sadelain, Dr. Maria Themeli talks to us about her work using stem cells to create killer T cells to seek and destroy cancer cells.
Resources and Links
Fat Isn't All Bad: Skin Adipocytes Help Protect Against Infections – Researchers report the surprising discovery that fat cells below the skin known as adipocytes help protect us from bacteria.
Researchers Target the Cell’s ‘Biological Clock’ in Promising New Therapy to Kill Cancer Cells, Shrink Tumor Growth – This article tells about the cell biologists at UT Southwestern Medical Center that have targeted telomeres with a small molecule called 6-thiodG that takes advantage of the cell’s "biological clock" to kill cancer cells and shrink tumor growth.
With Cancer, 'Bad Luck' of Random Mutations Is Largely to Blame – Scientists have created a statistical model that measures the proportion of cancer incidence, and have found that it's caused mainly by random mutations when stem cells divide.
Macrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells – Skin resident macrophages surround and signal to resting hair follicle stem cells, regulate their entry into a new phase of hair follicle growth.
Meth Users Face Higher Risk for Parkinson's Disease – This article reveals that people who use methamphetamine have a greatly increased risk of developing Parkinson's disease and that women who took the drug had higher odds of the disease than men.
Molecular Mechanism Behind Health Benefits of Dietary Restriction Identified – Findings from researchers suggest that hydrogen sulfide is one of the key molecules responsible for the benefits of dietary restriction or calorie restriction such as slowing aging and extending lifespan.
Decoding Fat Cells: Discovery May Explain Why We Gain Weight – Researchers discovered that a protein, Thy1, has a fundamental role in controlling whether a primitive cell decides to become a fat cell, making Thy1 a possible therapeutic target for obesity.
Egg and Sperm Race: Scientists Create Precursors to Human Egg and Sperm – Scientists at the University of Cambridge working with the Weizmann Institute have created primordial germ cells – cells that will go on to become egg and sperm – using human embryonic stem cells.
Billionaire Bought James Watson’s Nobel Prize Medal in Order to Return It – This article talks about Alisher Usmanov, the richest man in Russia and a major shareholder in Arsenal football club who has come forward as the buyer of James Watson’s Nobel Prize medal – declaring that he now plans to give the piece back and the money he spent on the item to be donated to scientific research.
Orangutan Inside Argentina Zoo Granted 'Non-Human Person Rights' in Landmark Ruling – In this article, an orangutan named Sandra held in an Argentinian zoo can be freed and transferred to a sanctuary after a court recognized the ape as a "non-human person" unlawfully deprived of its freedom.
Variation in Cancer Risk among Tissues Can Be Explained by the Number of Stem Cell Divisions – This article describes how Tomasetti and Vogelstein plotted the lifetime incidence of various cancers against the estimated number of normal stem cell divisions in the corresponding tissues over a lifetime, and found a strong correlation extending over five orders of magnitude.
New Technique for Bioengineering Stem Cells Shows Promise in HIV Resistance – According to this article, an improved gene therapy strategy using modified human stem cells shows promise in animal models as a functional cure for HIV.
lncRNA Maturation to Initiate Heterochromatin Formation in the Nucleolus Is Required for Exit from Pluripotency in ESCs – This article shows that maturation of the long noncoding RNA pRNA is required for establishment of heterochromatin at ribosomal RNA genes, the genetic component of nucleoli, and this process is inactivated in pluripotent ESCs.
Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced P...
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