Researchers at University of California San Diego have found that the most common form of liver cancer one with a high mortality rate can be better targeted and treated using an innovative new stem cell-derived therapy, according to a recently published study in Cell Stem Cell.
The treatment, not yet studied in patients, involves the lab engineering of natural killer (NK) cells white blood cells that destroy tumor cells to more effectively battle hepatocellular carcinoma (HCC), one of the most treatment-resistant types of solid tumor.
Genetically modified NK-cell therapy doesn't require personalization like chimeric antigen receptor (CAR)-expressing T-cell therapy a relatively new, personalized form of immunotherapy. That means an NK-cell therapy could be mass produced and shelf-ready for patients, who could begin therapy without delay, their new research shows.
To some extent all tumor cells perhaps hepatocellular carcinoma more so inhibit immune cells that try to kill them, said UC San Diego School of Medicine Professor Dan Kaufman, M.D., Ph.D., lead author on the study, director of the Sanford Advanced Therapy Center at the universitys Sanford Stem Cell Institute and Moores Cancer Center member.
This is one key reason why some immunotherapies like CAR T cells have been less successful for solid tumors than for blood cancers the immunosuppressive tumor microenvironment.
Kaufman and his team produced stem cell-derived NK cells in which the receptor for transforming growth factor beta (TGF-) a protein that impairs immune function was disabled. HCC tumors and the liver in general contain copious amounts of the substance, which both inhibits the immune cell activity and allows cancer to proliferate.
They found that typical NK cells without the disabled receptor, like CAR T cells, were not very effective in battling the cancer. These are pretty resistant tumors when we put them in mice, they grow and kill the mice, he said. The five-year survival rate for HCC in humans is less than 20 percent.
When researchers tested the modified NK cells against the cancer, however, we got very good anti-tumor activity and significantly prolonged survival, he noted.
These studies demonstrate that it is crucial to block transforming growth factor beta at least for NK cells, but I also think its true for CAR T cells, Kaufman said. If you unleash NK cells by blocking this inhibitory pathway, they should kill cancer quite nicely.
Kaufman anticipates that his teams discovery will manifest itself in the clinical trials of many research groups and companies whether theyre working on CAR T-cell or NK-cell therapies, battling hepatocellular carcinoma or other challenging types of solid tumors.
Anyone developing such therapies for solid tumors should be working to inhibit transforming growth factor beta activity to improve cancer-killing and attain effective anti-tumor activity, he said.
Co-authors of this study include Jaya Lakshmi Thangaraj; Michael Coffey; and Edith Lopez, all of the Division of Regenerative Medicine at UC San Diegos School of Medicine.
This work was made possible by the NIH/NCI grants U01CA217885, P30CA023100 (administrative supplement), and the Sanford Stem Cell Institute at the University of California San Diego.
Disclosures: Kaufman is a co-founder and advisor to Shoreline Biosciences and has an equity interest in the company. He also consults VisiCELL Medical and RedC Bio, for which he receives income and/or equity. Studies in this work are not related to work of those companies. The terms of these arrangements have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. The remaining authors declare no competing interest.
The UC San Diego Sanford Stem Cell Institute (SSCI) is a global leader in regenerative medicine and a hub for stem cell science and innovation in space. SSCI aims to catalyze critical basic research discoveries, translational advances and clinical progress terrestrially and in space to develop and deliver novel therapeutics to patients.
- More Stem Cells Extracted For Later Use For My MS [Last Updated On: March 14th, 2011] [Originally Added On: March 14th, 2011]
- Macular Degeneration Improved With Stem Cells [Last Updated On: April 2nd, 2011] [Originally Added On: April 2nd, 2011]
- Macular Degeneration Improved With Stem Cells [Last Updated On: April 3rd, 2011] [Originally Added On: April 3rd, 2011]
- Cells That Heal Us From Cradle To Grave: A Quantum Leap in Medical Science [Last Updated On: April 6th, 2011] [Originally Added On: April 6th, 2011]
- Stem Cell Patient Richard H. MS Treatment [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- STEM CELLS FOR MACULAR DEGENERATION Sam Smith's story.wmv [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- STEM CELLS FOR MACULAR DEGENERATION Sam Smith's story.wmv [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- Dr. Janet Rossant, Premier's Summit Award 2010 recipient [Last Updated On: May 31st, 2011] [Originally Added On: May 31st, 2011]
- Visions Episode 92: Stem Cells Discovery [Last Updated On: May 31st, 2011] [Originally Added On: May 31st, 2011]
- PROSTATE CANCER and stem cells.wmv [Last Updated On: June 9th, 2011] [Originally Added On: June 9th, 2011]
- Stem Cells Used to Grow Windpipes [Last Updated On: June 10th, 2011] [Originally Added On: June 10th, 2011]
- Visions Episode 92: Stem Cells Discovery [Last Updated On: July 12th, 2011] [Originally Added On: July 12th, 2011]
- PROSTATE CANCER and stem cells [Last Updated On: July 16th, 2011] [Originally Added On: July 16th, 2011]
- Doctors Use Stem Cells to Grow New Windpipes [Last Updated On: August 29th, 2011] [Originally Added On: August 29th, 2011]
- Sims 2 Mafia Story Part 7 - Farewell, Godfather/Stem Cell Medicine [Last Updated On: August 30th, 2011] [Originally Added On: August 30th, 2011]
- Regenerative Medicine: Pathways to Cure - Version 2.0 [Last Updated On: September 8th, 2011] [Originally Added On: September 8th, 2011]
- Stem Cell Research: Huntington's Disease [Last Updated On: September 10th, 2011] [Originally Added On: September 10th, 2011]
- Adult Stem Cell Therapy for COPD: One Man's Story [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- Stem Cell Update from Panama 3 Years Later [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Stem Cell Update from Panama 3 Years Later [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Regenerative Medicine and Applications of Stem Cell Research [Last Updated On: October 10th, 2011] [Originally Added On: October 10th, 2011]
- Stem Cell Therapy for Sickle Cell Anemia - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- Stem_Cell_Therapy_for_ALS.wmv - Video [Last Updated On: October 17th, 2011] [Originally Added On: October 17th, 2011]
- Spinal Cord Injury: Progress and Promise in Stem Cell Research - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Stem Cells: The Hope The Hype and the Science - Video [Last Updated On: October 22nd, 2011] [Originally Added On: October 22nd, 2011]
- What are stem cells? How can they be used for medical benefit? - Video [Last Updated On: October 24th, 2011] [Originally Added On: October 24th, 2011]
- What are stem cells? How can they be used for medical benefit? - Video [Last Updated On: October 25th, 2011] [Originally Added On: October 25th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - Stephen Huhn - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- The CIRM Creativity Awards: Training 21st Century Stem Cell Scientists - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- What Organ Shortage? Just Make Your Own! Stem Cells and Organ Engineering - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- StemEnhance is the Biggest Scientific Medical breakthrough of our time - World Exclusive! - Video [Last Updated On: November 9th, 2011] [Originally Added On: November 9th, 2011]
- StemEnhance is the Biggest Scientific Medical breakthrough of our time - World Exclusive! - Video [Last Updated On: November 10th, 2011] [Originally Added On: November 10th, 2011]
- Alumni Profile: Dr. John Tisdale, NIH Researcher, Stem Cell Transplants and Sickle Cell - Video [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- Intel co-founder Andrew Grove gives keynote at 2011 World Stem Cell Summit in Pasadena - Video [Last Updated On: November 16th, 2011] [Originally Added On: November 16th, 2011]
- Austin Forum - Nov 1st (Highlights) - Video [Last Updated On: November 17th, 2011] [Originally Added On: November 17th, 2011]
- Stem Cell Based Therapies for Blindness: David Hinton - CIRM Science Writer's Seminar - Video [Last Updated On: November 18th, 2011] [Originally Added On: November 18th, 2011]
- Dr. Jordan Pomeroy discusses xeno-Free Derivation and Maintenance of Pluripotent Cell Lines - Video [Last Updated On: November 19th, 2011] [Originally Added On: November 19th, 2011]
- So Many Chemicals...So Little Time: Stem Cell Research and Environmental Health - Video [Last Updated On: November 19th, 2011] [Originally Added On: November 19th, 2011]
- Austin Forum - Nov 1st (Part 4 of 4) - Video [Last Updated On: November 23rd, 2011] [Originally Added On: November 23rd, 2011]
- Austin Forum - Nov 1st (Part 2 of 4) - Video [Last Updated On: November 23rd, 2011] [Originally Added On: November 23rd, 2011]
- Austin Forum - Nov 1st (Part 1 of 4) - Video [Last Updated On: November 24th, 2011] [Originally Added On: November 24th, 2011]
- Alan Trounson: Are stem cells the end of disease? - Video [Last Updated On: November 29th, 2011] [Originally Added On: November 29th, 2011]
- Alan Trounson: Are stem cells the end of disease? - Video [Last Updated On: November 29th, 2011] [Originally Added On: November 29th, 2011]
- A4M Stem Cell Fellowship Module II Preview - Video [Last Updated On: December 1st, 2011] [Originally Added On: December 1st, 2011]
- Auxogyn_ASRM_FINAL.mov - Video [Last Updated On: December 2nd, 2011] [Originally Added On: December 2nd, 2011]
- Bruce Lipton,making the connections part 1 - Video [Last Updated On: December 3rd, 2011] [Originally Added On: December 3rd, 2011]
- Assessment of Embryo Viability (Auxogyn_ASRM_First Prize) - Video [Last Updated On: December 4th, 2011] [Originally Added On: December 4th, 2011]
- What is Cord Blood Banking? The Medical Potential of Newborn Stem Cells - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
- NAMCP 2011: Ravi Vij, MD, Associate Professor of Medicine, Washington University School of Medicine - Video [Last Updated On: December 9th, 2011] [Originally Added On: December 9th, 2011]
- StemCellTV Talks to Michael Werner of Alliance for Regenerative Medicine at Meeting on the Mesa - Video [Last Updated On: December 9th, 2011] [Originally Added On: December 9th, 2011]
- Future360 - Alan Trounson, CEO of the California Institute of Regenerative Medicine - Video [Last Updated On: December 9th, 2011] [Originally Added On: December 9th, 2011]
- 2011 World Stem Cell Summit Open Comments [Last Updated On: December 11th, 2011] [Originally Added On: December 11th, 2011]
- 2011 Summit: Keynote Address, CIRM's Translational Roadmap to Stem Cell Cures, Alan Trounson, PhD - Video [Last Updated On: December 14th, 2011] [Originally Added On: December 14th, 2011]
- 2011 Summit: Government [Last Updated On: December 14th, 2011] [Originally Added On: December 14th, 2011]
- Autism Stem Cell Trip - Video [Last Updated On: December 17th, 2011] [Originally Added On: December 17th, 2011]
- GeneCell International Dental Pulp Stem Cell's Banking Services - Video [Last Updated On: December 21st, 2011] [Originally Added On: December 21st, 2011]
- GeneCell International Dental Pulp Stem Cell's Banking Services - Video [Last Updated On: December 22nd, 2011] [Originally Added On: December 22nd, 2011]
- Dr Tony Talebi discusses stem cell transplantation in Myeloma with Dr Ratzan - Video [Last Updated On: January 2nd, 2012] [Originally Added On: January 2nd, 2012]
- Craig Venter: Understanding Our Genes - A Step to Personalized Medicine | CIRM Spotlight on Genomics - Video [Last Updated On: January 27th, 2012] [Originally Added On: January 27th, 2012]
- Craig Venter: Understanding Our Genes - A Step to Personalized Medicine | CIRM Spotlight on Genomics - Video [Last Updated On: January 28th, 2012] [Originally Added On: January 28th, 2012]
- Aesthetic Plastic Surgery / Anti Aging Medicine: The Next Generation Symposium Attracts a World Class Faculty to New ... [Last Updated On: January 28th, 2012] [Originally Added On: January 28th, 2012]
- Lecture by stem cell researcher tomorrow [Last Updated On: January 29th, 2012] [Originally Added On: January 29th, 2012]
- Biobanking for Medicine: Technology and Market 2012-2022 [Last Updated On: January 31st, 2012] [Originally Added On: January 31st, 2012]
- 'Personalized medicine' gets $67.5M research boost [Last Updated On: January 31st, 2012] [Originally Added On: January 31st, 2012]
- Clinical Trial for Myelofibrosis that Targets Cancer Stem Cells | CIRM Spotlight on Genomics - Video [Last Updated On: February 1st, 2012] [Originally Added On: February 1st, 2012]
- An Overview of Data Trends in Autologous Stem Cell Research and Clinical Use - James P. Watson, MD - Video [Last Updated On: February 1st, 2012] [Originally Added On: February 1st, 2012]
- An Overview of Data Trends in Autologous Stem Cell Research and Clinical Use - James P. Watson, MD - Video [Last Updated On: February 1st, 2012] [Originally Added On: February 1st, 2012]
- Dr. Ramaswamy on Targeting Dormant Cancer Cells - Video [Last Updated On: February 2nd, 2012] [Originally Added On: February 2nd, 2012]
- Daniel Kraft on Singularity 1 on 1 (part 3) - Video [Last Updated On: February 2nd, 2012] [Originally Added On: February 2nd, 2012]
- Daniel Kraft on Singularity 1 on 1 (part 1) - Video [Last Updated On: February 2nd, 2012] [Originally Added On: February 2nd, 2012]
- Statement - Rx&D Applauds Government of Canada for Investing in Personalized Medicine [Last Updated On: February 3rd, 2012] [Originally Added On: February 3rd, 2012]
- Molecules to Medicine: Plan B: The Tradition of Politics at the FDA [Last Updated On: February 3rd, 2012] [Originally Added On: February 3rd, 2012]
- 'Personalized medicine' gets $67.5M research boost [Last Updated On: February 3rd, 2012] [Originally Added On: February 3rd, 2012]
- The Pet Corner: Behold! The future of modern medicine is here [Last Updated On: February 4th, 2012] [Originally Added On: February 4th, 2012]
- Molecules to Medicine: Plan B: The Tradition of Politics at the FDA [Last Updated On: February 4th, 2012] [Originally Added On: February 4th, 2012]
- Treating Brain Injuries With Stem Cell Transplants - Promising Results [Last Updated On: February 4th, 2012] [Originally Added On: February 4th, 2012]
- Stem Cells to Treat Acne Scarring | Los Angeles | Hollywood | Beverly Hills - Video [Last Updated On: February 6th, 2012] [Originally Added On: February 6th, 2012]
- American CryoStem Completes Cell Processing for Clinical Study [Last Updated On: February 7th, 2012] [Originally Added On: February 7th, 2012]
- IntelliCell Demonstrates at the American Sports Medicine Institute Held in Conjunction with and at the Andrews Sports ... [Last Updated On: February 7th, 2012] [Originally Added On: February 7th, 2012]
- Meet the Founders of Cord Blood Registry - Video [Last Updated On: February 9th, 2012] [Originally Added On: February 9th, 2012]