Cancer Immunotherapy

Kidney Cancer

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Kidney cancer—also called renal cell 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 61,560 new cases of kidney cancer will be diagnosed in the U.S. in 2015, including cancer of the renal pelvis and Wilms tumor, a childhood cancer. There will be approximately 14,080 deaths. 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 92%. 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 12%.

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 five broad categories: checkpoint inhibitors and immune modulators, cancer vaccines, adoptive cell therapy, monoclonal antibodies, and cytokines. 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

A promising avenue of clinical research in kidney cancer is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances on immune responses. By blocking these inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses. The following trials are currently recruiting patients:

  • A phase III study of pembrolizumab (Keytruda, MK-3475), a PD-1 antibody being developed by Merck, in patients with advanced urothelial cancer, including the renal pelvis (NCT02256436).
  • A phase III study of nivolumab (Opdivo), a PD-1 antibody, with ipilimumab (Yervoy), a CTLA-4 antibody, both made by Bristol-Myers Squibb, versus sunitinib (Sutent), for patients with previously untreated advanced or metastatic renal cell carcinoma (NCT02231749).
  • A phase II study of MPDL3280A, a PD-L1 antibody being developed by Roche/Genentech, as monotherapy or in combination with Avastin (bevacizumab) versus sunitinib in patients with untreated advanced renal cell carcinoma (NCT01984242).  
  • Two phase I trials to test MPDL3280A in patients with several cancers (NCT01375842, NCT01633970).
  • A phase I study testing pembrolizumab (Keytruda, MK-3475) in patients with previously untreated advanced renal cell carcinoma (NCT02133742).
  • A phase I study testing pembrolizumab (Keytruda, MK-3475) in patients with advanced renal cell carcinoma (NCT02014636).
  • A phase I trial to test pembrolizumab (Keytruda, MK-3475) in patients with advanced, biomarker-positive solid tumors (NCT02054806).
  • A phase I trial of tremelimumab (anti-CTLA-4) and MEDI4736 (anti-PD-L1), made by MedImmune,  for patients with advanced solid tumors, including renal carcinoma (NCT01975831). This trial is sponsored by Ludwig Cancer Research in partnership with the Cancer Research Institute.
  • A phase I trial to test varlilumab (CDX-1127), an anti-CD27 antibody made by Celldex, in patients with several cancers, including renal cell cancer (NCT01460134).
  • A phase I study to test MGA217, an antibody that targets B7-H3, in patients with refractory cancer, including renal cell cancer (NCT01391143).
  • A phase I trial testing SGN-CD70A, an antibody that targets CD70, in renal cell cancer patients (NCT02216890).
  • A phase I study of lirilumab, a KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
  • A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1), in patients with solid tumors (NCT01968109).
  • A phase I trial testing urelumab, a 4-1BB/CD137 antibody, in patients with advanced cancers (NCT01471210).
  • A phase I study of MSB0010718C, a PD-L1 antibody being developed by EMD Serono, in solid tumors (NCT01772004).
  • A phase I trial of TRX518, a GITR antibody, in patients with advanced cancer (NCT01239134). This trial is sponsored by Ludwig Cancer Research in partnership with the Cancer Research Institute.
  • A phase I trial of MK-4166, a GITR antibody, in patients with advanced cancer (NCT02132754).

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, being developed by Argos Therapeutics, plus standard treatment for patients with advanced renal cell carcinoma (ADAPT) (NCT01582672).
  • A phase I/II trial of DCVax, being developed by Northwest Biotherapeutics, in patients with solid tumors (NCT01882946).
  • A phase I study of vaccine therapy with or without sirolimus in treating patients with NY-ESO-1 expressing solid tumors (NCT01522820).

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.

  • A phase I/II study treating metastatic cancer, including renal cancer, with anti-VEGFR2 gene engineered CD8+ cells (NCT01218867).
  • A phase I trial to test natural killer (NK) cells, important innate immune cells, in patients with advanced cancer, including kidney cancer (NCT00720785).

Monoclonal Antibodies

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Several monoclonal antibodies are currently being tested in clinical trials:

  • A phase II trial of ASONEP (sonepcizumab, LT1009), a monoclonal antibody that binds to and inhibits the function of sphingosine-1-phosphate (S1P), which promotes blood-vessel formation (angiogenesis), in patients unresectable and refractory renal cell carcinoma (NCT01762033).
  • A phase I/II trial of TRC105, an antibody targeting endoglin, which is a protein that is overexpressed on endothelial cells and is essential for angiogenesis, in patients with advanced or metastatic renal cell carcinoma (NCT01806064).
  • A phase I/II trial testing LY2875358, an antibody targeting mesenchymal-epithelial transition factor (MET), which is involved in tumor cell proliferation and resistance, in patients with advanced cancer, including renal cell carcinoma (NCT02082210).
  • A phase I/II trial testing IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with epithelial cancers, including renal cell carcinoma (NCT01631552).

Cytokines

Cytokines are messenger molecules that help control the growth and activity of immune system cells.

  • A phase I trial of AM0010, a recombinant human interleukin 10 (IL-10), in patients with advanced solid tumors, including renal cell carcinoma (NCT02009449).
  • A phase I study testing interleukin 15 (IL-15) in patients with selected cancers, including kidney cancer (NCT01727076).
  • A phase I trial testing interleukin 15 (IL-15) in patients with advanced cancer (NCT01572493).
  • A phase I trial to test interleukin 12 (IL-12) in patients with solid tumors (NCT01417546).


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 Clinic and Laboratory Integration Program (CLIP) grant from CRI to study the metabolism of kidney cancer 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. But kidney cancer needs glucose too, and this shared need for glucose fosters competition for nutrients within the tumor that may suppress anti-tumor immunity.  These studies may provide a new way to augment anti-tumor immunity by manipulating glucose metabolism. His work also suggests that therapies designed to block immune checkpoints, such as anti-PD-1 antibodies, may act in part by shifting this metabolic competition back in favor of immune cells.

Sources: National Cancer Institute Physician Data Query (PDQ); American Cancer Society Facts & Figures 2015; ClinicalTrials.gov; CRI documents

Reviewed and updated March 2015


[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)

 

Kidney Cancer News & Stories

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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