Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Patients’ cells from tumors, the immune system merged for customized cancer therapy

15.07.2004


One of the strongest natural allies that cancer patients can tap to help fight tumor growth and metastasis may well be their own immune systems, and scientists affiliated with the Harvard University Medical School have devised ways of bolstering patients’ immune response against kidney and breast cancer.



In a paper published in the July 15 issue of the journal Clinical Cancer Research, the Harvard research team documented tumor regression in two breast cancer patients, and stabilization and containment of tumor growth in late stage breast and kidney patients through application of customized vaccinations made from the patients’ own tumor and immune system cells.

By fusing patients’ tumor cells with their immune system dendritic cells, researchers associated with the laboratory of Donald Kufe, M.D., professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, created customized antigen-presenting immune cells that train T cells to hunt, recognize and destroy the patients’ tumor cells.


"We aimed to develop a novel vaccine that took whole tumor cells with their complete array of tumor-specific antigens and combine them with the potent immune stimulating machinery of the dendritic cells," said David Avigan, M.D., director of bone marrow transplantation at Beth Israel Deaconess Medical Center, and the lead author of the Clinical Cancer Research article.

The immune system develops T cells, which are white blood cells, to recognize foreign proteins, cells, and other matter that causes disease or infection. Tumor cells produce proteins, carbohydrates and other molecules that are different than the healthy cells that are normally found in the human body. The immune system can recognize cancer-related molecules, but cancer cells often are difficult for the immune system to detect. Conversely, dendritic cells are potent immune stimulating cells capable of generating the type of T Cells that attack and kill cancer cells.

In the past, immunologists have attempted to define cancer specific markers and develop vaccinations with those molecules, but most tumors don’t have well-defined antigens that can be isolated or have proved useful for vaccination development. Previous research approaches often were aimed at producing T cells that would recognize a defined cancer marker molecule, but the immune response to those vaccinations often fell short of expectations.

The Harvard team aimed at making a hybrid cell composed of both the cancer cells and dendritic cells taken from patients for use exclusively in the individual from whom the cells were obtained.

"This approach increased the number of antigens that immune system cells can recognize," Avigan said. "And for the individual patients, those antigens are specific to their own tumor cells."

The challenges of the trial included constructing the hybrid cells and evaluating the vaccinations performance in the donor patients. The dendritic cells were obtained from the patients’ blood. But harvesting cells from the tumors proved difficult. Cell numbers from individual patients were sometimes too low for successful generation of the hybrid tumor/dendritic cell fusion.

The study group included 23 patients--10 people with breast cancer and 13 with kidney cancer--from whom the researchers were able to collect enough cells to construct fusion cells in the laboratory. The effect of the vaccine on the patient’s immune system was measured by the number of circulating T cells that reacted with the patient-derived tumor cells before and after vaccination. Vaccination induced a doubling of tumor reactive T cells in about half the 18 patients in which this was measured. Ten patients doubled the percentage of CD4+ T cells that produced interferon gamma, a cytokine integral to the immune response. Seven patients doubled the percentage of CD8+ T cells that produced the interferon in response to exposure to the tumor.

"The increase of these interferon-producing T cells indicated that the fusion cell vaccination was promoting a heightened response by the immune system," Avigan said. "That response was targeted at antigens on the tumor cells."

The vaccine was well tolerated with only minimal toxicity observed. While a potential concern with vaccine therapy is the induction of an immune response against normal tissues of the body, no evidence of significant autoimmunity was seen.

A third of the study participants responded positively to the customized therapy. Among the breast cancer patient to be immunized, one woman responded to the trial vaccination with 80 percent regression of her chest wall tumor mass within a month. After four months, the tumor had regressed by 90 percent. She remained stable with no evidence of progression during the following two years. A second patient responded with regression of half a tumor that had spread to her adrenal gland, and almost half a pulmonary nodule as well. That individual showed resumed disease progression after a half year. A third breast cancer patient, and five kidney cancer patients, remained stable for three to nine months after completion of the vaccination treatments.

"The results from this patient group, while preliminary, hold promise that fusion cell technology may emerge as an effective immunotherapeutic strategy allowing patients to use their own immune system to fight their cancer," Avigan said.

While the results were not universal to all the study participants, Avigan said that that further development of the vaccination, and application on patients with less advanced disease and whose immune systems were less severely weakened, may increase the positive results observed in the Harvard group’s initial Phase I trail.

Kufe’s and Avigan’s colleagues in the study were comprised of researchers from two Harvard Medical School teaching affiliates, the Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center.

Russell Vanderboom | EurekAlert!
Further information:
http://www.aacr.org

More articles from Health and Medicine:

nachricht Laser activated gold pyramids could deliver drugs, DNA into cells without harm
24.03.2017 | Harvard John A. Paulson School of Engineering and Applied Sciences

nachricht What does congenital Zika syndrome look like?
24.03.2017 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>