Promising results in immunotherapy
Professor Håkan Mellstedt is a medical oncologist at the Cancer Center Karolinska in Sweden, with extensive clinical and academic experience. In this article, Prof. Mellstedt, also a member of our Scientific Committee, explains the basics of immunotherapy and key research being conducted across cancer types.
What is immunotherapy?
Immunotherapy is very attractive option for cancer treatment, because it empowers the defense mechanism of the patients in order to destroy cancer cells.
After years of slow progress, immunotherapy has now accelerated and clinical trials are finally producing some very interesting results.
Types of immunotherapy
Immunotherapies against existing cancers include:
- Active immunotherapy: This type of immunotherapy increases the ability of the patient’s immune system to recognize antigens which are associated to the tumor and therefore to eliminate malignant cells.
- Passive immunotherapy: This is the administration of components that have been produced outside of the body (such as lymphocytes or antibodies) that can destroy cancer cells.
- Immunomodulation: This treatment type includes agents that are not specific to any type of cancer, but enhance the general immune responsiveness and amplify the anticancer immune response.
Immunotherapies are being extensively studied in clinical trials across a variety of cancers. The most important newly published data and drugs approval as well as promising research results are presented below.
Representation of an antibody
In April 2010, the US FDA approved the Sipuleucel-T treatment (active immunotherapy) for patients with advanced prostate cancer that is refractory to hormones, who are experiencing minimal symptoms.
The approval of Sipuleucel-T was based largely on the results of the “IMPACT” trial. This trial showed a median overall survival of 25.8 months for patients treated with the vaccine, compared with 21.7 months for those who did not receive it.
Novel agents against specific proteins (like the PD-L1 and the PD-1) (immunomodulation) are under intensive investigation, some of which have been approved.
Preliminary results from several studies have shown promising or impressive efficacy as second-line treatment in advanced non-small cell lung cancer. Several phase 3 studies are underway, and their results are awaited with great interest.
Several vaccines (active immunotherapy) have been tested with unclear results. The most important is the therapeutic vaccine designed to induce immune response to cancer cells expressing the MUC1 protein. Only a subgroup of patients who had received combined chemo-radiotherapy seems to benefit. Similarly, the Belagenpumatucel-L vaccine improved the survival in a few subgroups of patients.
A clinical trial focused on active immunotherapy directed against patients with HER2 advanced breast cancer. The trial results showed that this immunotherapy might have a great benefit only in women with low levels of HER2 expression.
There is intensive research in this field, including another study trying to combine this active immunotherapy with Trastuzumab (passive immunotherapy).
Melanoma is a malignant tumor with a high sensitivity to immunotherapy. Several vaccines have developed to treat this type of cancer.
Agents targeting specific proteins like the CTLA-4 (immunomodulation) and the PD-1 protein (such as Ipilimumab and Nivolumab, respectively) are the most active. These agents have contributed to the significant improvement in the treatment of advanced malignant melanoma.
Furthermore, the B-RAF protein and the MEK enzyme are also an area of interest as targets for immunotherapy in melanoma
It is also important to mention that in early disease, Interferon in high doses (immunomodulation) remains the most effective adjuvant treatment.
Pancreatic and Colorectal Cancer
For pancreatic cancer, the therapeutic target has been the mutation in the “KRAS” gene, which is present in 90% of this type of cancer. Therefore, the ongoing trials are based on immunization with specific KRAS derived mutated peptides.
A vaccine under investigation for pancreatic cancer is called “Alpenpantucel-L”.
For colorectal cancer, vaccination is based on e.g. the so-called “CarcinoEmbryonic Antigen (CEA)”. Research is ongoing.
Renal Cell Carcinoma
Researchers are currently investigating a promising vaccine under the name
“AGS-003” in combination with Sunitinib, for renal cell carcinoma. Another combination under research is the novel vaccine called “IMA901” (synthesized tumor derived peptides) in combination with Sunitinib. Results will be presented soon.
Impressive results have also been presented using anti-PD1 antibodies (immunomodulation).
It must be mentioned that for the treatment of advanced renal cancer, oncologists use Interferon (mainly) and Interleukin (more rarely) (immunomodulation).
Conclusions for immuno-oncology
Immunotherapy is an established therapeutic option for cancer patients, and has been proven effective in the fight against various cancers. Scientists are continuing their research on such treatments, and the results so far have been promising.
Among the early research and clinical findings indicate that immunotherapy is more effective in patients with low tumor burden, in other words against tumors with small overall volume. Although it is not immediately effective, but may last for long periods.
Certainly, all this research in immunotherapy against cancer marks an era of great excitement for a new class of treatments that can help patients overcome their disease.
Prof. Håkan Mellstedt, MD, PhD