REFERENCES:

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
  2. Abbas AK, Lichtman HH. Basic Immunology. 3rd ed. Saunders. 2011.
  3. Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4(6):905-913.
  4. Le Mire L, Hollowood K, Gray D, Bordea C, Wojnarowska F. Melanomas in renal transplant recipients. Br J Dermatol. 2006;154(3):472-477.
  5. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol. 2006;6(11):836-848.
  6. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329-360.
  7. Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203-213.
  8. Sato E, Olson SH, Ahn J, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102(51):18538-18543.
  9. Galon G, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960-1964.
  10. Van Houdt IS, Sluijter BJ, Moesbergen LM, et al. Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression. Int J Cancer. 2008;123(3):609-615.
  11. Kirkwood JM, Butterfield LH, Tarhini AA, et al. Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012;62(5):309-335.
  12. Boikos SA, Antonarakis ES. Immunotherapy for prostate cancer enters its golden age. Clin Med Insights Oncol. 2012;6:263-273.
  13. Pohlmann PR, Mayer IA, Mernaugh R. Resistance to Trastuzumab in Breast Cancer. Clin Cancer Res. 2009;15(24):7479-7491.
  14. Cheson BD, Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin's lymphoma. N Engl J Med. 2008;359(6):613-626.
  15. Ribas A. Tumor immunotherapy directed at PD-1. N Engl J Med. 2012;366(26):2517-2519.
  16. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723.
  17. Lotze M, et al. In: Cancer: Principles & Practice of Oncology. 9th ed. 2011.
  18. Gulley JL. Therapeutic vaccines: the ultimate personalized therapy? Hum Vaccin Immunother. 2013;9(1):219-221.
  19. Risk M, Corman JM. The role of immunotherapy in prostate cancer: an overview of current approaches in development. Rev Urol. 2009;11(1):16-27.
  20. Gulley JL, Drake CG. Immunotherapy for prostate cancer: recent advances, lessons learned, and areas for further research. Clin Cancer Res. 2011;17(12):3884-3891.
  21. Murphy K. Janeway’s Immunobiology. 8th ed. New York, NY: Garland Science, Taylor & Francis Group, LLC; 2012.
  22. Ribas A, Butterfield LH, Glaspy JA, Economou JS. Current developments in cancer vaccines and cellular immunotherapy. J Clin Oncol. 2003;21:2415-2432.
  23. Sharma P, Wagner K, Wolchok JD, Allison JP. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps. Nat Rev Cancer. 2011;11:805-812.
  24. Disis ML, Wallace DR, Gooley TA, et al. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. J Clin Oncol. 2009;27(28):4685-4692.
  25. Ribas A, Timmerman JM, Butterfield LH, Economou JS. Determinant spreading and tumor responses after peptide-based cancer immunotherapy. Trends Immunol. 2003;24(2):58-61.
  26. Lechleider RJ, Arlen PM, Tsang KY, et al. Safety and immunologic response of a viral vaccine to prostate-specific antigen in combination with radiation therapy when metronomic-dose interleukin 2 is used as an adjuvant. Clin Cancer Res. 2008;14(16):5284-5291.
  27. Gulley JL, Arlen PM, Bastian A, et al. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res. 2005;11(9):3353-3362.
  28. Inderberg-Suso E-M, Trachsel S, Lislerud K, Rasmussen AM, Gaudernack G. Widespread CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001. OncoImmunology. 2012;1(5):670-686.
  29. Madan RA, Gulley JL, Fojo T, Dahut WL. Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression. Oncologist. 2010;15(9):969-975.
  30. Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550-4557.
  31. Prieto PA, Yang JC, Sherry RM, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res. 2012;18(7):2039-2047.
  32. Kakimi K, Nakajima J, Wada H. Active specific immunotherapy and cell-transfer therapy for the treatment of non-small cell lung cancer. Lung Cancer. 2009;65:1-8.
  33. Kantoff PW, Schuetz TJ, Blumenstein BA, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099-1105.
  34. Hammarlund E, Lewis MW, Hansen SG, et al. Duration of antiviral immunity after smallpox vaccination. Nat Med. 2003;9(9):1131-1137.
 

Important Safety Information:

 

Malignant tumors develop in individuals with compromised immune systems3,4

Fold-increase in tumor/cancer risk in transplant patients compared to general population

Please rate this chart based upon relevance.





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Welcome to an Interactive Exploration of:

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The importance of the immune system’s interaction with cancer

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How immunotherapy empowers the patient’s defense system

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How immunotherapy fights cancer on 3 different fronts

Content created and developed by Dendreon

This session will take approximately
3 to 5 minutes of your time.

At the end of your session, you will be offered the opportunity to:

  • Receive a monograph about cancer immunotherapy
  • Receive an immunotherapy slide deck to share with your peers
  • Request additional information

First let’s explore the interaction
between the immune system and cancer.

  • Cancer may result from a breakdown of the immune system1
  • The immune system is recognized as having a critical role in controlling cancer1,2
  • Diminished immune system function is associated with an increased risk of cancer2

The dynamic balance between the
immune system and cancer.

On one side, the immune system is capable of protecting the individual by blocking tumor growth, development, and survival. On the other side, the cancer cells are able to evade detection by the immune system (via numerous mechanisms) and grow.5

The dynamic balance between the
immune system and cancer.

This dynamic relationship is demonstrated here using a seesaw analogy, with immune protection (or the ability of the immune system to protect the individual) on the left and immune evasion (or the ability of the cancer to evade detection by the immune system) on the right. This relationship will be discussed further in the next several slides.

The shifting of this balance consists of 3 phases: Elimination, Equilibrium,
and Escape.

Elimination: Eradication of cancer cells
Elimination refers to the phase in which cancer cells are identified and effectively eradicated by the immune system.

In this phase, the balance is shifted in favor of immune protection.5,6

Equilibrium: Proliferation and elimination
The Equilibrium phase is entered in the event that the immune system is not able to completely eliminate all cancer cells but can control or prevent further growth or spreading of the abnormal cells.5,6

Escape: Evasion of the immune system
In the Escape phase, the conceptual seesaw tips in favor of immune evasion, leading to progressive disease.5,6

If you are seeing markers of cancer progression, what phase of that dynamic balance between the immune system and cancer is taking place?

You are correct!

Through multiple evasion techniques, cancer cells can avoid elimination and eventually ESCAPE from immune control.5,6

100%

of your peers answered correctly

Now let’s explore the immune response and the key cells involved.

The immune response begins with antigen-presenting cells (APCs) responding to foreign antigens in the body, such as the antigens on cancer cells. These APCs then become activated.2

Adapted from Abbas K, et al.2

The immune response and the key cells involved.

Then the APCs present the foreign antigens to naive T cells, which activates those T cells.2

Adapted from Abbas K, et al.2

The immune response and the key cells involved.

These T cells replicate and specialize into effector T cells, which either directly target and kill cancer cells or activate other immune cells, such as B cells that create antibodies against tumor antigens.2

Adapted from Abbas K, et al.2

The immune response and the key cells involved.

Some activated T cells may specialize into memory cells, priming the immune system to respond to that antigen if it is encountered again.2

Adapted from Abbas K, et al.2

T cell infiltration within tumors is associated with
overall survival (OS) in patients with certain cancers.7-10

Please rate this chart based upon relevance.

Which immune cells have been shown to infiltrate certain tumors (a finding associated with increased overall survival)?

You are correct!

T CELL infiltration within tumors is associated with overall survival (OS) in patients with certain cancers (as seen in the Kaplan-Meier curve for OS in advanced ovarian cancer).7

100%

of your peers answered correctly

Let’s focus on types of immunotherapy, and how they carry on the fight.

The timing of the treatment may affect the outcome.

  • Relative efficacy of immunotherapy may be greater with lower tumor burden11,19
  • Patient given immunotherapy earlier in disease course might have a better outcome20
  • Below is a graphic demonstrating the theoretical understanding of why earlier treatment with immunotherapy may improve patient outcomes20

Please rate this chart based upon relevance.

--- Expected clinical outcome

     if no treatment is provided

† = Death

A = Patient given a vaccine earlier

B = Patient given a vaccine later


Adapted with permission from Gulley JL, et al.20

Theoretically, immunotherapy may be more effective at what stage of metastatic disease?

You are correct!

The efficacy of immunotherapy may be greater when TREATED EARLIER in the disease course with a LOWER TUMOR BURDEN.11,18,20

100%

of your peers answered correctly

Immunotherapy's 3-prong assault on cancer

(Explore each area below to proceed)

SPECIFIC

Immunotherapy builds a population of immune cells
over time that specifically target cancer cells2,21

ADAPTABLE

The activated immune system adapts as cancer mutates,
enabling it to recognize new tumor antigens11,21-28

DURABLE

The immune system has memory and remains primed
to stimulate a tumor-specific response2,16,18,21,28

Which of the 3 key attributes would be important in the presence of mutating cancer cells?

You are correct!

Immunotherapy allows the immune system to be ADAPTABLE to subsequent cancer mutations.18

100%

of your peers answered correctly

REVIEW

The dynamic balance between the immune system and cancer can make the difference between the elimination and growth of cancer cells.


Immunotherapy

  • Specifically targets cancer cells
  • Creates an immune response that may adapt to recognize new antigens
  • May deliver durable effects even after treatment is completed

It can change the trajectory of the disease and slow the progression of the cancer over time.

Immunotherapy should be considered an option for the treatment of cancer in appropriate patients.

Has this session increased the likelihood that you would use immunotherapy as treatment for your cancer patients?

NO, NOT AT ALL

YES, VERY MUCH

We appreciate your feedback.

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Please select any or all of the following as thanks for your participation in this interactive session:

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Thank you for completing this interactive session.


To learn more about immunotherapy, visit:

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©2013 Dendreon Corporation. All rights reserved. May 2013. MA-05.13.83.00