Immunotherapy heralds ‘new era’ for cancer treatment.
International trial using ipilimumab and nivolumab to treat patients with advanced melanoma stopped cancer advancing in 58% of cases. Recently presented at the 2015 American Society for Clinical Oncology annual meeting:
one study revealed that a drug combination of ipilimumab and nivolumab (an immune therapy drug) reduced tumor size in almost 60% of individuals with advanced melanoma – the deadliest form of skin cancer – compared with ipilimumab alone,
while another study found nivolumab reduced the risk of lung cancer death by more than 40%.
Sources and more information
Immunotherapy heralds ‘new era’ for cancer treatment,MedicalNewsToday, 4 June 2015.
Trials show immune drugs effective in advanced melanomas, eurekalert, 1-JUN-2015.
Immunotherapy drug improves survival for common form of lung cancer, eurekalert, 31-MAY-2015.
Doctors and researchers are constantly looking for ways to improve treatments
Treating cancers with immunotherapy and radiotherapy at the same time could stop them from becoming resistant to treatment, according to a study published in Cancer Research.
The researchers, based at The University of Manchester and funded by Cancer Research UK and MedImmune found that combining the two treatments helped the immune system hunt down and destroy cancer cells that were not killed by the initial radiotherapy in mice with breast, skin and bowel cancers.
Sources and more information:
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade, Cancer Research, October 1, 2014 74;5458.
Immunotherapy could stop resistance to radiotherapy, Cancer Research UK Press release, 1 October 2014.
Potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin
A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian cancer and mesothelioma. Investigators from the Massachusetts General Hospital (MGH) Vaccine and Immunotherapy Center report in the Journal of Hematology & Oncology that a protein engineered to combine a molecule targeting a tumor-cell-surface antigen with another protein that stimulates several immune functions prolonged survival in animal models of both tumors.
Read Antigen-targeting fusion protein should be less expensive, more accessible than current approaches, MGH News Release, 05/Mar/2014
A novel mycobacterial Hsp70-containing fusion protein targeting mesothelin augments antitumor immunity and prolongs survival in murine models of ovarian cancer and mesothelioma
Although dendritic cell (DC) vaccines are considered to be promising treatments for advanced cancer, their production and administration is costly and labor-intensive. We developed a novel immunotherapeutic agent that links a single-chain antibody variable fragment (scFv) targeting mesothelin (MSLN), which is overexpressed on ovarian cancer and mesothelioma cells, to Mycobacterium tuberculosis (MTB) heat shock protein 70 (Hsp70), which is a potent immune activator that stimulates monocytes and DCs, enhances DC aggregation and maturation and improves cross-priming of T cells mediated by DCs.
Binding of this fusion protein with MSLN on the surface of tumor cells was measured by flow cytometry and fluorescence microscopy. The therapeutic efficacy of this fusion protein was evaluated in syngeneic and orthotopic mouse models of papillary ovarian cancer and malignant mesothelioma. Mice received 4 intraperitoneal (i.p.) treatments with experimental or control proteins post i.p. injection of tumor cells. Ascites-free and overall survival time was measured. For the investigation of anti-tumor T-cell responses, a time-matched study was performed. Splenocytes were stimulated with peptides, and IFNγ- or Granzyme B- generating CD3+CD8+ T cells were detected by flow cytometry. To examine the role of CD8+ T cells in the antitumor effect, we performed in vivo CD8+ cell depletion. We further determined if the fusion protein increases DC maturation and improves antigen presentation as well as cross-presentation by DCs.
We demonstrated in vitro that the scFvMTBHsp70 fusion protein bound to the tumor cells used in this study through the interaction of scFv with MSLN on the surface of these cells, and induced maturation of bone marrow-derived DCs. Use of this bifunctional fusion protein in both mouse models significantly enhanced survival and slowed tumor growth while augmenting tumor-specific CD8+ T-cell dependent immune responses. We also demonstrated in vitro and in vivo that the fusion protein enhanced antigen presentation and cross-presentation by targeting tumor antigens towards DCs.
This new cancer immunotherapy has the potential to be cost-effective and broadly applicable to tumors that overexpress mesothelin.
Sources and full Research
Journal of Hematology & Oncology /content/7/1/15 2014, 7:15 doi:10.1186/1756-8722-7-15
Leading cancer research centers team up to launch biotech startup focused on cancer immunotherapy
The Fred Hutchinson Cancer Research Center (“The mission of Fred Hutchinson Cancer Research Center is the elimination of cancer and related diseases as causes of human suffering and death.”) and Memorial Sloan-Kettering Cancer Center (“At Memorial Sloan-Kettering Cancer Center (MSK), we’re committed to exceptional patient care, research, and education.”), along with pediatric partner Seattle Children’s Research Institute (“Proud to be one of the top children’s hospitals & pediatric research institutes in the US. Supported by a generous community, like you. Hope. Care. Cure.”), have joined forces to launch Juno Therapeutics Inc., a new biotechnology company focused on bringing forward novel immunotherapies for cancer.