Cancer Immunotherapy

Kidney Cancer

Kidney cancer—also called renal cancer—is one of the major types of cancer for which new immune-based cancer treatments are currently in development. This page features information on kidney cancer and immunotherapy clinical trials for kidney cancer patients, and highlights the Cancer Research Institute’s role in working to bring effective immune-based cancer treatments to kidney cancer patients.

 

BRIEF STATISTICS

Approximately 63,920 new cases of kidney cancer will be diagnosed in the U.S. in 2014, including cancer of the renal pelvis and Wilms tumor, a childhood cancer. There will be approximately 13,860 deaths. The incidence of kidney cancer cases has been increasing since the late 1990s, possibly due to earlier detection, while the death rate has been going down. Kidney cancer is more common in older people (>55 years old) and affects men more often than women.


The kidney is the organ that filters blood, cleaning out wastes and making urine. About 9 out of every 10 kidney cancers are renal cell carcinomas—cancers that form in the lining of the tubules inside the kidney. A person can live with only one functioning kidney.


In its early stages, kidney cancer typically has no symptoms. As a tumor grows, symptoms may include blood in the urine, pain or a lump in the lower back or abdomen, fatigue, weight loss, and swelling in the ankles or legs. If kidney cancer is diagnosed while the cancer is still local (has not spread beyond the kidney), the 5-year survival rate is 91%. Often a tumor will be discovered when a patient has a CT scan or ultrasound for another reason. Like most cancers, kidney cancer is difficult to treat once it has spread to other parts of the body. Metastatic kidney cancer has a 5-year-survival rate of less than 10%.

Risk factors for kidney cancer include tobacco use, obesity, high blood pressure, chronic renal failure, exposure to certain industrial chemicals, such as trichloroethylene, and radiation.

Most renal cell carcinomas are a subtype called clear cell carcinoma. About 7 out of 10 people with renal cell carcinoma have this kind of cancer.

 

KIDNEY CANCER TREATMENT

Surgery is the primary treatment for most kidney cancers. Many surgeries can be performed laparoscopically, i.e., through a minimally invasive surgical procedure. Ablation therapy using either heat or cold to destroy the tumor may be an option for patients who are not good candidates for surgery. Kidney cancer tends to be resistant to both chemotherapy and radiation therapy. Therefore, targeted therapies and immune-based treatments are important components of treatment for advanced kidney cancer.

Several targeted therapies have been approved by the FDA for use in advanced kidney cancer. These include drugs such as bevacizumab (Avastin) and sunitinib (Sutent), which stop the growth of the new blood vessels that nourish cancers; and temsirolimus (Torisel) and everolimus (Afinitor), which block a protein called mTOR. Targeted therapies are often the first line of treatment for advanced kidney cancer. Chemotherapy is generally used only after targeted therapies and immunotherapies have already been tried.

 

WHEN ARE CLINICAL TRIALS RECOMMENDED?

Currently available treatments for kidney cancer are less than optimal. Therefore, enrolling in a clinical trial is often the best and safest option for patients with kidney cancer.

For a complete list of open clinical trials for kidney cancer, see our Clinical Trial Finder.

 

IMMUNOTHERAPY FOR KIDNEY CANCER

The first suggestion that kidney cancer might be a good target for immunotherapy came from the observation that patients with metastatic kidney cancer occasionally experienced spontaneous regressions after surgical removal of the primary tumor.[1] Immunotherapies in the form of immune-stimulating chemicals called cytokines have been used for more than a decade to treat kidney cancer. The cytokines interleukin-2 (IL-2) and interferon-alpha cause kidney cancers to shrink in approximately 10%-20% of patients, and provide durable remissions in a subset of these patients. In the recent past, IL-2 was the most common first-line therapy for advanced kdiney cancer, but because it can have serious side effects many doctors now only use it for cancers that are not responding to targeted therapies.

Beyond cytokines and targeted therapies, several newer immunotherapies are becoming important in the treatment of kidney cancer. They fall into three broad categories: checkpoint inhibitors, cancer vaccines, and adoptive cell therapy. These therapies for kidney cancer are still in clinical testing, but their successful use in other types of cancers suggests that they may ultimately prove beneficial for kidney cancer patients as well.

Checkpoint Inhibitors

These drugs work by targeting molecules that serve as brakes on the immune response. By blocking these inhibitory molecules, checkpoint inhibitors are designed to unleash or enhance pre-existing anti-cancer immune responses. This promising new approach was envisioned by CRI Scientific Advisory Council director James P. Allison, Ph.D., who developed the first checkpoint inhibitor, ipilimumab (anti-CTLA-4), for the treatment of metastatic melanoma. Several clinical trials of checkpoint inhibitors are currently enrolling patients:

  • A phase III study of nivolumab (anti-PD-1) vs. everolimus in pre-treated advanced or metastatic clear cell renal cell carcinoma (NCT01668784).
  • A phase II study of MPDL3280A (anti-PD-L1) as monotherapy or in combination with Avastin (bevacizumab) versus sunitinib in patients with untreated advanced renal cell carcinoma (NCT01984242).  
  • A phase II study of CT-011 (anti-PD-1) alone or with dendritic cell/renal cell carcinoma fusion cell vaccine (NCT01441765).
  • A phase I study of ipilimumab (anti-CTLA-4) in children and adolescents with treatment-resistant cancer (NCT01445379).
  • A phase I trial of tremelimumab (anti-CTLA-4) and MEDI4736 (anti-PD-L1) used in combination for patients with advanced solid tumors (NCT01975831). This trial is sponsored jointly by the CRI/Ludwig Clinical Trials Network. Patients with advanced solid tumors, including renal carcinoma, are eligible for the trial.

Cancer Vaccines

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Several clinical trials are ongoing: 

  • A phase III trial of dendritic cell immunotherapy (AGS-003) plus standard treatment of advanced renal cell carcinoma (RCC) (ADAPT) (NCT01582672).
  • A phase III study of IMA901 cancer vaccine in patients receiving sunitinib as first-line therapy for advanced/metastatic renal cell carcinoma (NCT01265901). Note: this trial is ongoing but not currently enrolling patients.
  • A phase II study of CT-011 (anti-PD-1) alone or with dendritic cell/renal cell carcinoma fusion cell vaccine (NCT01441765).

Adoptive Cell Therapy

In this approach, immune cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several clinical trials are currently enrolling patients:

  • A phase II study of chemotherapy followed by NY-ESO-1 lymphocytes and aldesleukin to treat metastatic cancer (NCT00670748).
  • A phase I/II study treating metastatic cancer with anti-VEGFR2 gene engineered CD8+ lymphocytes (NCT01218867). 
     

 

CRI CONTRIBUTIONS AND IMPACT

CRI has a long history of supporting research that has improved the treatment of kidney cancer, from research on IL-2 and interferon to current treatment approaches using checkpoint blockade. In 1978, Jordan Gutterman, M.D., received funding from CRI to conduct a clinical trial of interferon-alpha in human patients. The study showed that kidney cancer is sensitive to interferon and paved the way for the FDA approval of this treatment.[2]

In 1993, CRI researchers Drew Pardoll, M.D., Ph.D., Glenn Dranoff, M.D., Elizabeth Jaffee, M.D., Hyam Levitsky, M.D., and colleagues conducted preclinical studies showing that a vaccine composed of tumor cells irradiated and genetically modified to produce immune system growth factor GM-CSF (granulocyte macrophage colony-stimulating factor) could induce potent, specific, and long-lasting anti-tumor immunity in multiple mouse tumor models. Based on these preclinical findings, CRI provided funding for a phase I clinical trial to test the vaccine in patients with metastatic renal cell carcinoma. This work led to the therapeutic cancer vaccine GVAX.

In 1999, CRI researchers including Neil Bander, M.D., Dirk Jäger, M.D., Elke Jäger, M.D., Alexander Knuth, M.D., and Lloyd J. Old, M.D., used SEREX technology to identify tumor-associated antigens in patients with renal cell carcinoma.[3] This work provided an important foundation for the idea that renal cancer is immunogenic—able to be recognized by the immune system.

In 2010, CRI researchers Drew Pardoll, M.D., Ph.D., Susan Topalian, M.D., and colleagues completed a phase I study showing that a PD-1-specific monoclonal antibody induces frequent tumor regressions in patients with advanced melanoma, renal cancer, lung cancer, and colon cancer with very low rates of toxicity. This study helped establish that PD-1 blockade is a promising new therapy for multiple types of cancers, including ones for which currently approved therapies are not effective.[4]

In 2012, Jeffrey Rathmell, Ph.D., of Duke University Medical Center, Durham, NC, was awarded a CLIP grant from CRI to study the metabolism of renal tumor cells and the immune cells that surround them. Rathmell and colleagues have shown that T cells that mediate anti-tumor immunity are highly dependent on glucose. If access to glucose is limited, T cells fail to function and instead can become regulatory T cells that suppress immunity. Clear cell renal cell carcinoma (ccRCC) is defined by a genetic defect that promotes high levels of glucose consumption. This shared need for glucose among both anti-tumor lymphocytes and renal tumor cells fosters competition for nutrients within the tumor that may suppress anti-tumor immunity, and may be one reason why the immune system fails to defeat renal cancer. These studies may provide a new way to augment anti-tumor immunity by manipulating glucose metabolism.

 

Sources: National Cancer Institute Physician Data Query (PDQ); American Cancer Society Facts & Figures 2014; ClinicalTrials.gov.

 

Reviewed and updated March 2014.



[1] Jennifer Cudris and Jaime R. Merchan. “Immunotherapy in Renal Carcinoma, in Advances in Tumor Immunology and Immunotherapy. Current Cancer Research 2014, pp 125-147.

[2] Gutterman JU, Fine S, Quesada J, Horning SJ, Levine JF, Alexanian R, Bernhardt L, Kramer M, Spiegel H, Colburn W, Trown P, Merigan T, Dziewanowski Z. Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. Ann Intern Med 1982 May; 96: 549-556. (PMID: 6176159)

[3] Scanlan, M. J., Gordan, J. D., Williamson, B., Stockert, E., Bander, N. H., Jongeneel, V., Gure, A. O., Jäger, D., Jäger, E., Knuth, A., Chen, Y.-T. and Old, L. J. Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int. J. Cancer 1999; 83: 456–464. (PMID: 10508479)

[4] Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010 Jul 1; 28: 3167-3175. (PMID: 20516446)

 

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Reviewed By:

Elke Jäger, M.D.
Elke Jäger, M.D.
Krankenhaus Nordwest, Frankfurt, Germany

Reviewed By:

Alexander Knuth, M.D.
Alexander Knuth, M.D.
National Center for Cancer Care & Research, Qatar

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