Immunotherapy (from The Clearity Foundation newsletter)

Alexandra

Immunotherapy offers a woman battling ovarian cancer a way to further personalize her cancer treatment using her own immune system to attack the tumor.  Some of these immunotherapies are generated by using live tumor tissue that has to be properly saved at the time of surgery, so it is critical to know the requirements for such clinical trials beforehand. There are many immunotherapy options and choosing among them is still not easy.  The results to date are from early stage clinical trials where small numbers of women were treated.  In addition, there are no tests to predict who is most likely to benefit from these treatments.  But, the early data are promising and as soon as such tests are available in CLIA/CAP-accredited laboratories, we will incorporate them into the Clearity profile.  For the immunotherapy agents given in combination with chemotherapy in these clinical trials, the Clearity molecular profile can be helpful to prioritize among them on the basis of the chemotherapy tests. 

Clinical Trial Eligibility Criteria: Viable tumor tissue   In addition to your cancer status, the number of prior treatments you've had, and your health and performance status, the availability of fresh tumor tissue is an important criterion for some clinical trials.  For many of the new therapies that aim to stimulate your own immune system to attack your tumor cells, you must provide fresh tumor from a recent surgery or biopsy.  Cells from your tumor are used to prepare a personalized vaccine (see Immunotherapies for Ovarian Cancer article below) and therefore must be alive to be used by the lab that makes the vaccine.   Typical surgical or biopsy procedures are generally followed by "fixing" the tumor in formalin.  While this preserves the tissue so it can be evaluated by a pathologist and can be used for Clearity profiling, it also kills the cells so that they cannot be used for production of such vaccines.  Therefore, it is important to plan ahead by talking with your doctor about potential vaccine trials for which you may be eligible before you have surgery.  That will ensure that some of your tumor is saved and either shipped directly to the lab while the cells are alive or preserved in a way that it can be "resurrected" from a frozen state.  Thinking ahead will ensure that you are prepared to take advantage of these immunotherapy approaches in the future.

Check out the new clinical trials results section on Clearity's website. This helpful tool summarizes and tabulates the results from clinical trials being performed in ovarian cancer. Click here to see how these new agents measure up.

Immunotherapies for Ovarian Cancer     The human immune system is very powerful. Successfully harnessing the immune system to destroy tumors, cancer immunotherapy, has been a dream of many oncologists. Cancer immunotherapy has become a reality with sipuleucel-T (Provenge) for prostate cancer, ipilumumab (Yervoy) for melanoma, and adaptive T cell therapy in treating some leukemias and lymphomas. Recent immunotherapy approaches for ovarian cancer are showing more promise than in the past.  These approaches include (1) vaccines, (2) treatment with the patient's own immune cells - adaptive T-cell transfer, and (3) immune check point inhibitors, drugs that remove a brake on the immune system that may be protecting tumor cells. Combinations of new vaccine strategies with chemotherapy and/or adaptive T-cell transfer approaches have made the furthest inroads against ovarian cancer and are the focus of this article.  They are being evaluated in women who are newly diagnosed (as maintenance after front line treatment) as well as in women who have recurrent cancer.   A vaccine is a treatment that "teaches" the immune system what the enemy looks like and hence what to fight against. For example, the familiar flu vaccine exposes the recipient to something that looks very much like the flu. Once exposed to the flu vaccine, the body knows what flu looks like and prepares an arsenal of weapons to attack anything that closely resembles what was in the vaccine.  Vaccine therapies against cancer also "teach" the immune system to recognize the tumor as an invader. Once educated, the body can mount an attack against the tumor. Some tumor vaccines are made from proteins expressed primarily on tumors, known as tumor-specific antigens. Vaccines created from tumor-specific antigens are known as protein or peptide vaccines. Other vaccines are made from the patient's own tumor collected at surgery, a completely personalized (autologous) vaccine.  Combination of a protein vaccine with chemotherapy Promising results from a Phase 1 ovarian cancer trial using a protein vaccine were published in the January edition of Cancer Immunology Research. The tumor-specific antigen, or protein, used to create the vaccineis NY-ESO-1. This study showed the potential of a protein vaccine approach combined with chemotherapy (doxorubicin) and a drug (decitabine) to improve the visibility of the cancer cells to the newly educated immune cells.   Dr. Kunle Odunsi of the Roswell Park Cancer Institute, the principle investigator of this study, pointed out that although the purpose of this phase I trial was to assess safety, clinical benefit was seen in up to 60 percent of patients with chemotherapy resistant tumors.  Personalized vaccine There are currently 22 actively recruiting "vaccine ovarian cancer" trials listed at ClinicalTrials.gov. Nine of these are Phase 2 trials.  The FANG(TM) personalized ovarian tumor vaccine is among the tumor cell vaccines that is furthest along in the development process, having already been tested in Phase 1 and 2 trials with Phase 3 trials planned.  (Click here to review a previous newsletter to learn more about the differences between Phase 1, 2, and 3 trials) This vaccine utilizes the patient's own tumor cells, which are modified in the laboratory to express an immune-stimulatory molecule (GM-CSF) and to block expression of an immune-inhibitory molecule (TGF-b). Recently released results from a randomized phase 2 study (NCT01309230) in high risk stage III/IV ovarian cancer patients presented at the American Society for Gene Therapy meeting, May 2013, demonstrated promising outcomes in the patients treated to date.  In the interim study analysis, patients who received the vaccine plus standard of care chemotherapy took more than twice as long for the cancer to progress (470 days; 10 patients) as those who received only chemotherapy (193 days; 5 patients).  While promising, the number of patients in this analysis is small and these effects need to be demonstrated in a larger number of women so we will be on the lookout for the final analysis of this Phase 2 study.  Combination of personalized vaccines and adaptive T-cell transfer Another approach to personalized vaccine production is to use the patient's blood AND  tumor cells to create a vaccine. Key cells for triggering an immune response, called dendritic cells, are isolated from the blood and then exposed to an extract from the tumor cells in the lab.  Exposure to the tumor extract allows these dendritic cells to become "teacher" cells for the rest of the immune system. These teacher cells, injected back into the patient, make up the vaccine. Once in the body, these newly educated dendritic cells recruit other immune cells to mount an attack against the tumor. Cytotoxic T Lymphocytes (CTL) are among the most effective immune cells recruited by the dendritic cells for attack.  The educated and attacking CTLs can now be isolated from the blood, expanded in number in the laboratory, and then re-injected into the patient. This process is known as adaptive T-cell transfer.  Immunotherapy approaches are experimental, but early clinical trial data suggest the potential for real benefit. Immunotherapy by its nature is highly personalized. A Clearity patient has the opportunity to find a trial that fits her personal molecular profile and potentially leverages her very unique immune system.

Explore Your Clinical Trial Options Using the Clearity Search Engine   Finding clinical trials can be a challenge when you don't know how or where to begin.  One approach is to use the results from your Clearity Tumor Blueprint to find drugs that match and are in clinical trials.  These can be trials that combine a chemotherapy drug prioritized by your profile with a new agent or a targeted therapy being tested in a clinical trial for the first time.    Click here for a search engine tutorial and click here to start using the clinical trial search engine.

If you have a Clearity Tumor Blueprint, we want to hear from you!    As you know, each biomarker (test) in the tumor molecular profile is there because it is associated with response to the drugs commonly used or in clinical trials for ovarian cancer treatment.  The evidence for each of the tests can be found on our website (http://www.clearityfoundation.org/healthcare-pros/drugs-and-biomarkers.aspx). That evidence comes from clinical research studies carried out in ovarian and other cancers.     We would like to increase the amount of evidence for ovarian cancer by using the results from your Clearity profile (in an anonymous way of course), but to do that, we need to know how your profile was used by your doctor to select your treatment (we need you to arrange to have your oncology flowsheets sent to us for that)-and most importantly, how you are doing.  We are regularly in touch with some of you but would like to hear from everyone. We believe that your contribution to this analysis may help you (if needed in the future) and can also help others.  Please contact us at info@clearityfoundation.org or at 858-657-0282 to tell us how you are and learn how you can help in this effort.

 

kimberly sue 63

My surgery was two years

My surgery was two years ago...I doubt they saved any tissu

ovarian_support

kimberly sue 63 said:

My surgery was two years

My surgery was two years ago...I doubt they saved any tissu

I think they did.

When we went in to consult with my mom's oncologist we asked about where they would get the tissue or if they would have to do another surgery.  He said that they preserved all of it in a paraffin wax block and that it would be around long after we all were gone for future study.  I don't know if this is standard procedure across the country or just out our hospital, but you can always check.  Good luck.

lovesanimals

ovarian_support said:

I think they did.

When we went in to consult with my mom's oncologist we asked about where they would get the tissue or if they would have to do another surgery.  He said that they preserved all of it in a paraffin wax block and that it would be around long after we all were gone for future study.  I don't know if this is standard procedure across the country or just out our hospital, but you can always check.  Good luck.

Interesting!

Thank you for sharing, Alexandra. 

Kelly

2timothy1 7

Thanks for researching and

Thanks for researching and posting!