+353-1-416-8900REST OF WORLD
+44-20-3973-8888REST OF WORLD
1-917-300-0470EAST COAST U.S
1-800-526-8630U.S. (TOLL FREE)

PRINTER FRIENDLY

Cancer Immunotherapy: immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapies - Overview

  • ID: 3066973
  • Report
  • September 2014
  • Region: Global
  • 141 Pages
  • Insight Pharma Reports
This report focuses on the rising potential for the newest and most promising of cancer treatments: cancer immunotherapy. Cancer immunotherapy was once just a dream in the minds of physicians, clinicians and patients, but only recently (2010s era) has it actually been within reasonable reach. Cancer Immunotherapy: immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapies covers three principle therapies that have been in the works for cancer patients.

One principle therapy that has been on the rise is checkpoint inhibitors. Checkpoint inhibitors are a class of monoclonal antibodies that inhibit pathways responsible for blocking the response of T-cells to antigens. Not only have results from clinical trials of these therapeutics been promising, but treatments have already been approved both in the U.S. and Europe for metastatic melanoma. There are several agents and targets covered in this section, including the September 5, 2014 approval of Merck's PD-1 inhibitor: pembrolizumab (Keytruda), as well as the future outlook of potential combination checkpoint inhibitor therapies.

Another principle therapy under investigation are anticancer vaccines. This is another major strategy surfacing in cancer therapeutics and, unlike traditional vaccines which are given to prevent illness (i.e. smallpox, measles, and pertussis), these vaccines are given to patients who already have cancer and are designed to elicit an antitumor response to even the most aggressive of cancers. Though this is a theoretically good approach to combat cancer, there have been an unfortunate number of clinical failures and the industry has gained only one U.S. approved anticancer vaccine. Combination therapies are also a possible route these vaccines will take in the future.

Finally, the last therapy addressed in this report is adoptive cellular immunotherapy. Adoptive cellular immunotherapy is when syngeneic activated T-cells are infused in patients to attack their cancers. There are a few types of cellular immunotherapies including: tumor infiltrating lymphocyte (TIL) therapy, genetically engineered T cells bearing chimeric antigen receptors (CARs), and recombinant TCR technology. Improving these therapies is the goal over the next few years and researchers have been working heavily to commercialize these products and technologies.

The report is further coupled with an in-depth introduction and history as well as with data for market outlook. Also featured in this report are exclusive interviews with three high-end professors, researchers and CEOs:

- Adil Daud, MD, Clinical Professor, Department of Medicine (Hematology/Oncology), University of California at San Francisco (UCSF); Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center.

- Matthew Lehman, Chief Executive Officer, Prima BioMed (a therapeutic cancer vaccine company with headquarters in Sydney, Australia).

- Marcela Maus, MD, PhD, the Director of Translational Medicine and Early Clinical Development, Translational Research Program, Abramson Cancer Center, University of Pennsylvania in Philadelphia.

Furthermore, survey was conducted which analysed the data representing a population sample from the R&D industry. This survey depicts market outlook, and portrays industry opinions and perspectives.
Note: Product cover images may vary from those shown
Executive Summary
Checkpoint inhibitors
Therapeutic anticancer vaccines
Adoptive immunotherapy for cancer

- TIL therapy
- Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
- Recombinant TCR technology
- The future of adoptive immunotherapy for cancer

Outlook for cancer immunotherapy

CHAPTER 1: Introduction
The early history of cancer immunotherapy
Cytokines as immunomodulatory drugs

- Interleukin-2
- Alpha-interferons
- Interleukin-12
- Interleukin-12 as a bridge between innate and adaptive immunity
- Investigation of interleukin-12 as an anticancer therapeutic

CHAPTER 2: Checkpoint Inhibitors
What are immune checkpoints?
CTLA-4 blocking agents

- Ipilimumab
- Tremelimumab

PD-1 blocking agents

- Nivolumab
- Nivolumab in NSCLC
- Combination therapy of nivolumab plus ipilimumab in melanoma
- Pembrolizumab (Merck’s Keytruda)
- PD-L1 expression as a biomarker for response to pembrolizumab in melanoma and in NSCLC
- Merck’s strategy for development and approval of pembrolizumab
- Other anti-PD-1 agents

PD-L1 blocking agents

- Roche/Genentech’s MPDL3280A
- MPDL3280A in NSCLC
- MPDL3280A in urothelial bladder cancer
- MedImmune/AstraZeneca’s MEDI4736
- Medarex/BMS’s MDX-1105

Are there other clinical-stage checkpoint inhibitors on the horizon?
Discussion of the Adil Daud interview
Conclusions
Interview with Adil Daud, MD

CHAPTER 3: Therapeutic anticancer vaccines
Introduction
Cancer vaccines- a field rife with clinical failures

- Why has the cancer vaccine field been so prone to clinical failure?

Marketed and selected late-stage cancer vaccines in development

- Dendreon’s sipuleucel-T (APC8015, Provenge)
- Talimogene laherparepvec (Amgen’s T-Vec)
- Celldex’ rindopepimut (CDX-110)
- Tecemotide (Oncothyreon/Merck Serono)
- PROSTVAC-VF (Bavarian Nordic)
- AGS-003 (Argos Therapeutics)
- CVac (Prima BioMed)
- Cancer vaccine failure the result of poor clinical trial design?

Conclusions
Interview with Matthew Lehman

CHAPTER 4: Adoptive Immunotherapy for Cancer
Introduction
Adoptive immunotherapy with tumor infiltrating lymphocytes (TILs)

- A specific immunodominant mutation in a melanoma patient who had a durable complete remission due to TIL therapy
- Adoptive immunotherapy based on mutation-specific CD4+ T cells in an epithelial cancer
- Commercializing TIL therapy

Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)

- University of Pennsylvania/Novartis’ CD19-targeting CAR T-cell therapy CTL019 (formerly CART19)
- Pilot studies of CTL019
- Later studies of CTL019
- Commercialization of CTL019 therapy
- The Marcela Maus interview and CTL019
- Juno Therapeutics’ 19-28z CD19-targeting CAR T-cell therapy
- Serum cytokine levels and safety of 19-28z CAR T-cell immunotherapy
- Efficacy of 19-28z CAR T-cell therapy in patients with CD19+ malignancies
- Can CAR T-cell therapy be applied to treatment of solid tumors?
- CAR T-cell therapy targeting mesothelin on malignant pleural mesothelioma and pancreatic cancer
- CAR T-cell therapy targeting GD2 on neuroblastoma
- Other companies developing CAR-based immunotherapies

Recombinant TCR technology

- Adaptimmune
- Autologous recombinant TCR therapies under investigation in Dr. Steven Rosenberg’s group at the NCI

Market issues
Interview with Marcela Maus, MD, PhD

CHAPTER 5: Summary and Conclusions
Checkpoint inhibitors
Therapeutic anticancer vaccines
Adoptive immunotherapy for cancer

- TIL therapy
- Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
- Recombinant TCR technology
- The future of adoptive immunotherapy for cancer

Insight Pharma Reports survey on cancer immunotherapy

Outlook for cancer immunotherapy

References
Note: Product cover images may vary from those shown

Loading
LOADING...

The regular use of immunotherapy for treatment of cancer, which had been an elusive dream for over 100 years, has very recently become within the grasp of researchers, physicians, and patients. As of the early-to-mid 2010s, cancer immunotherapy has become a "hot" area, with intense competition between biotechnology and pharmaceutical companies to be the first to market the newest, most effective therapies.

This report focuses on the three principal types of therapeutics that have become the major focuses of research and development in cancer immunotherapy (which is often called "immuno-oncology") in recent years:

- Checkpoint inhibitors (discussed in Chapter 2)
- Therapeutic anticancer vaccines (discussed in Chapter 3)
- Adoptive cellular immunotherapy (discussed in Chapter 4)

The report also includes a survey on adoptive immunotherapy for cancer, which was conducted by Insight Pharma Reports in conjunction with this report, and is discussed in Chapter 5.

Also included are three expert interviews with the following people:

- Adil Daud, MD, Clinical Professor, Department of Medicine (Hematology/Oncology), University of California at San Francisco (UCSF); Director, Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center.
- Matthew Lehman, Chief Executive Officer, Prima BioMed (a therapeutic cancer vaccine company with headquarters in Sydney, Australia).
- Marcela Maus, MD, PhD, the Director of Translational Medicine and Early Clinical Development, Translational Research Program, Abramson Cancer Center, University of Pennsylvania in Philadelphia.

Chapters 2-5 are preceded by an introductory Chapter 1, which focuses on the history of cancer immunotherapy, and the use of cytokines as immunotherapies for cancer. Although the use of high-dose interleukin-2 as an immunotherapy for advanced melanoma and kidney cancer has fallen out of favor in recent years due to the toxicity of the agent and the need for specialized treatment centers, there are researchers who are attempting to revive and improve this treatment. This is because IL-2 is the only drug (as opposed to cellular therapies) so far that has produced any durable complete responses in patients with metastatic melanoma or metastatic RCC. Moreover, the type of specialized treatment centers needed for IL-2 therapy may also constitute the best solution for delivery of certain types of cellular therapies. Researchers are also working to develop novel types of cytokine-based immunotherapies for cancer, such as OncoSec’s locally administered IL-12-based gene therapy. Thus the field of cytokine-based immunotherapies is far from dead.

Nevertheless, cytokine- based immunotherapies have limited utility, and do not command the excitement of the three more recently developed modes of therapy discussed in Chapters 2, 3, and 4.
Note: Product cover images may vary from those shown
Adroll
adroll