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 Research offers clues for improved influenza vaccine design
09.04.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Injecting gene cocktail into mouse pancreas leads to humanlike tumors
06.04.2018 | University of Texas Health Science Center at San Antonio

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: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>