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癌免疫療法:臨床転帰改善のための初期の成功からのさらなる飛躍

Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes

発行 Insight Pharma Reports 商品コード 504305
出版日 ページ情報 英文 218 Pages
納期: 即日から翌営業日
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癌免疫療法:臨床転帰改善のための初期の成功からのさらなる飛躍 Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes
出版日: 2017年04月30日 ページ情報: 英文 218 Pages
概要

当レポートでは、癌免疫治療薬の開発動向を調査し、免疫チェックポイント阻害剤、癌ワクチン、養子T細胞療法など主要薬剤クラスにおける開発・承認、上市の状況、主要製品の概要、主要企業の取り組み、将来の展望などをまとめています。

エグゼクティブサマリー

第1章

  • イントロダクション
  • 癌免疫療法の初期の経緯:Coley毒素
  • 免疫調整薬としてのサイトカイン
  • インターロイキン-2
  • αインターフェロン
  • インターロイキン-12
  • 先天性免役・適応免疫間のブリッジとしてのインターロイキン-12
  • 抗癌剤としてのインターロイキン-12の調査
  • インターロイキン-10
  • インターロイキン-15
  • Admune/Novartisのヘテロ二量体IL-15:IL-15Rα (hetIL-15)
  • AltorのALT-803
  • 総論:サイトカインベースの癌免疫治療薬

第2章

  • 免疫チェックポイントとは
  • CTLA-4遮断薬
  • イピリムマブ
  • トレメリムマブ
  • PD-1遮断薬
  • ニボルマブ
  • メラノーマにおけるニボルマブ+イピリムマブの併用療法
  • ペンブロリズマブ
  • 進行NSCLCの第一選択薬としてのペンブロリズマブ
  • ミスマッチ修復欠損大腸癌におけるペンブロリズマブ
  • 併用免疫治療におけるペンブロリズマブの研究
  • PDR001
  • PD-L1遮断薬
  • アテゾリズマブ
  • 尿路上皮癌の治療におけるアテゾリズマブ
  • NSCLCの治療におけるアテゾリズマブ
  • その他の固形腫瘍の治療におけるアテゾリズマブ
  • その他の抗PD-L1 mAb剤
  • デュルバルマブ
  • アベルマブ
  • 抗LAG-3剤
  • 抗TIM-3
  • NewLink Genetics:小分子IDO系経路阻害剤・チェックポイント阻害
  • Infinity:腫瘍の免疫抑制調整のためのPI3Kγ阻害剤IPI-549
  • チェックポイント阻害療法のためのバイオマーカー
  • 標的バイオマーカー
  • 遺伝子バイオマーカー
  • 免疫バイオマーカー
  • チェックポイント阻害剤による治療におけるバイオマーカー検査の利用
  • チェックポイント阻害剤+放射線治療
  • チェックポイント阻害剤+標的治療
  • チェックポイント阻害剤+細胞毒性化学療法
  • ディスカッション

第3章

  • 免疫アゴニスト
  • Celldex Therapeuticsのバルリルマブ (CDX-1127)
  • OX40アゴニスト
  • MedImmune/AZのOX40アゴニストプログラム
  • Roche/GenentechのOX40アゴニストプログラム
  • Nektar Therapeutics/BMSのNKTR-214, CD122アゴニスト
  • グルココルチコイド誘導性TNFR関連 (GITR) タンパク質アゴニスト (Leap TherapeuticsのTRX518)
  • 総論

第4章

  • 二重特異性抗体
  • 上市済み二重特異性抗体製剤
  • カツマキソマブ
  • ブリナツモマブ
  • CAR-T細胞の代替としての二重特異性抗体
  • Xencor:クロスリンクモノクローナル抗体 (XmAb) 二重特異性プラットフォーム技術
  • Regeneron:天然ヒト免疫グロブリンフォーマットbsAb, REGN1979
  • Roche/Genentech
  • MacroGenicのMGD007
  • 総論、など

第5章

  • 抗癌ワクチン・腫瘍溶解性ウイルス
  • イントロダクション
  • 癌ワクチン:臨床的失敗例の多い分野
  • 上市済み癌ワクチン・腫瘍溶解性ウイルス療法
  • Dendreon/Valeant:sipuleucel-T
  • Amgen:タリモジーンラハーパレプベック (T-Vec)/Imlygic
  • 臨床開発中の癌ワクチン・腫瘍溶解性ウイルス
  • Celldex:CDX-1401
  • Bavarian Nordic:PROSTVAC-VF
  • Argos Therapeutics:AGS-003
  • Sydys Corporation:CVac
  • Aduro Biotech:CRS-207
  • TapImmune:TPIV110 HER2/neu・TPIV200葉酸受容体アルファマルチエピトープワクチン
  • GeneluxのGL-ONC1腫瘍溶解性ウイルス
  • 総論、など

第6章

  • 癌の養子免疫療法
  • イントロダクション
  • 腫瘍浸潤性リンパ球と養子免疫療法
  • 上皮癌の変異特異的CD4+ T細胞に基づく養子免疫療法
  • TIL療法の商業化
  • CAR T細胞ベースの免疫療法の主要臨床プログラム
  • Kite Pharma:KTE-C19 (axicabtagene ciloleucel)
  • Novartis:CTL019
  • Juno:JCAR015・その他の抗CD19 CAR
  • 血液悪性腫瘍をターゲットとするその他のCAR T細胞療法
  • bluebird bio:多発性骨髄腫向けbb2121
  • 固形腫瘍をターゲットとするCAR T細胞療法
  • Novartis/University of Pennsylvania:CARTmeso
  • EGFRvIII CAR T細胞療法
  • Bellicum Pharmaceuticals:CAR T細胞療法の調整技術
  • Cellectis:「オフザシェルフ」CAR T細胞治療薬の設計・製造技術
  • CAR T細胞療法の製造上の課題
  • Adptimmune:遺伝子組換えTCRの臨床的候補
  • Kite Pharma:遺伝子組換えTCRプログラム
  • Juno Therapeutics:遺伝子組換えTCRプログラム
  • NCIにおける遺伝子組換えTCRの研究
  • 総論
  • T細胞療法の市場規模推計、など

第7章

  • 総論
  • 本レポートの主要テーマ:免疫腫瘍学2.0 (あるいは免疫腫瘍学の第二波)
  • チェックポイント阻害剤の承認
  • チェックポイント阻害剤のバイオマーカー
  • 承認済み・臨床段階の免疫生物製剤 (チェックポイント阻害剤以外)
  • TIL細胞による免疫療法
  • TIL療法の商業化
  • CAR T細胞療法の製造における課題
  • 自家遺伝子組換えTCR技術による養子免疫療法
  • 細胞免疫療法の進歩:一般的総論
  • 癌免疫療法の展望
  • 参考文献、など
目次

This new report builds on our 2014 Insight Pharma Report, Cancer Immunotherapy: Immune Checkpoint Inhibitors, Cancer Vaccines, and Adoptive T-cell Therapies. In that report, we focused on the major classes of cancer immunotherapy drugs that were then emerging from academic and corporate research: immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapies. This new report includes an updated discussion of approved and clinical stage agents in immuno-oncology, including recently-approved agents. It also addresses the means by which researchers and companies are attempting to build on prior achievements in immuno-oncology to improve outcomes for more patients. Some researchers and companies refer to this approach as “immuno-oncology 2.0.” The American Society of Clinical Oncology (ASCO), in its 12th Annual Report on Progress Against Cancer (2017), named “Immunotherapy 2.0” as its “Advance of the Year.”

Moreover, treatment of advanced melanoma (the cancer for which the largest amount of data on immunotherapy has been amassed) with checkpoint inhibitors has in some cases produced spectacular results. For example, data released at the May 2016 ASCO Annual Meeting indicate that 40% of metastatic melanoma patients who received pembrolizumab (Merck's Keytruda) in a large clinical trial are still alive three years later. is represents a substantial improvement over just a few years ago, when the average survival time for patients with advanced melanoma was measured in months. Nevertheless, metastatic melanoma remains incurable. Furthermore, in many studies in advanced melanoma and other cancers, only a minority of patients have benefited from immunotherapy treatments. Researchers and companies are therefore looking for ways to build on the initial successes of the immuno-oncology field to improve outcomes for more patients, hence the need for an “immuno-oncology 2.0.” Agents that are intended to improve the results of treatment with agents like checkpoint inhibitors may also be referred to as “second-wave” immuno-oncology agents.

As discussed in this report, researchers have found that checkpoint inhibitors produce tumor responses by reactivating TILs (tumor infiltrating lymphocytes)-especially CD8+ cytotoxic T cells. This key observation is perhaps the most important factor driving development of second-wave immuno-oncology strategies. As a result, researchers have been developing biomarkers that distinguish inflamed (i.e., TIL-containing) tumors-which are susceptible to checkpoint inhibitor therapy-from “cold” tumors, which are not. They have also been working to develop means to render “cold” tumors inflamed, via treatment with various conventional therapies and/or development of novel agents. These studies are the major theme of “second-wave” immuno-oncology, or “immuno-oncology 2.0.”

Highlights of this Report Include:

  • Approvals of checkpoint inhibitors
  • Biomarkers for checkpoint inhibitor treatments
  • Approved and clinical-stage immunotherapy biologics other than checkpoint inhibitors
  • Immunotherapy with TIL cells
  • Commercialization of TIL therapy
  • Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
  • Manufacturing issues with CAR T-cell therapies
  • General conclusions on the progress of cellular immunotherapy
  • Outlook for cancer immunotherapy

What you will Learn:

  • Why is immuno-oncology important, in terms of advancing cancer treatment beyond the traditional modalities of chemotherapy, radiation therapy, and surgery? What is immuno-oncology 2.0, and how might it advance the field of cancer immunotherapy?
  • What are the major classes of current and emerging immuno-oncology therapeutics?
  • How do these agents work?
  • Which immuno-oncology drugs have been approved? Which late-stage agents are likely to reach the market in the next 5 years? How might these newer agents benefit patients?
  • How are researchers, physicians, and companies attempting to achieve improved results with immuno-oncology treatments, in terms of increasing the numbers of patients who benefit from these treatments, achieving improved patient survival, and treating previously untreatable and incurable types of cancer?
  • Why has there been such a high rate of failure in the field of therapeutic anticancer vaccines? How are researchers and companies attempting to use immuno-oncology 2.0 strategies to reduce the numbers of failures, and thus to benefit patients?
  • Why is neoantigen science important in immuno-oncology, especially in development of novel vaccines and cellular immunotherapies? Which academic research groups, and established and emerging companies, are developing neoantigen-based therapies?
  • What are the cellular immunotherapy products that are emerging in 2017? What are the issues in manufacturing cellular immunotherapy products, and in administering them to patients safely? Why has it been difficult to commercialize tumor infiltration lymphocyte (TIL) therapies, despite their success in treating metastatic melanoma?
  • What is the expected market size for cancer immunotherapy in the 2017-2024 period? How might that market size be affected by the entry of new immuno-oncology 2.0 agents, and of cellular immunotherapy products?

Biomarkers for Use in Clinical Studies of Checkpoint Inhibitors:

TABLE OF CONTENTS

EXECUTIVE SUMMARY

  • Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes
  • Approvals of checkpoint inhibitors
  • Biomarkers for checkpoint inhibitor treatments
  • Approved and clinical-stage immunotherapy biologics other than checkpoint inhibitors
  • Immunotherapy with TIL cells
  • Commercialization of TIL therapy
  • Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
  • Manufacturing issues with CAR T-cell therapies
  • Adoptive immunotherapy via autologous recombinant TCR technology
  • General conclusions on the progress of cellular immunotherapy
  • Outlook for cancer immunotherapy
  • About Cambridge Healthtech Institute

CHAPTER 1:

  • Introduction
  • The early history of cancer immunotherapy - Coley's toxins
  • 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
  • Interleukin-10
  • Interleukin-15
  • Admune/Novartis' heterodimeric IL-15:IL-15Rα (hetIL-15)
  • Altor's ALT-803
  • Conclusions: Cytokine-based immunotherapies for cancer

CHAPTER 2:

  • What are immune checkpoints?
  • CTLA-4 blocking agents
  • Ipilimumab
  • Tremelimumab
  • PD-1 blocking agents
  • Nivolumab
  • Combination therapy of nivolumab plus ipilimumab in melanoma
  • Pembrolizumab
  • Pembrolizumab as a first-line treatment for advanced NSCLC
  • Pembrolizumab in colorectal carcinoma with mismatch-repair deficiency
  • Studies of pembrolizumab in combination immunotherapies
  • PDR001
  • PD-L1 blocking agents
  • Atezolizumab
  • Atezolizumab in treatment of urothelial carcinoma
  • Atezolizumab for the treatment of NSCLC
  • Atezolizumab in treatment of other solid tumors
  • Other anti-PD-L1 mAb agents
  • Durvalumab
  • Avelumab
  • Anti-LAG-3 agents
  • anti-TIM-3
  • NewLink Genetics' small-molecule IDO pathway inhibitors and checkpoint inhibition
  • Infinity's PI3Kγ inhibitor IPI-549 for modulation of immune suppression in tumors
  • Biomarkers for checkpoint inhibitor treatments
  • Target biomarkers
  • Genetic biomarkers
  • Immunological biomarkers
  • Use of biomarker tests in treatment with checkpoint inhibitors
  • Checkpoint inhibitors plus radiation therapy
  • Checkpoint inhibitors plus targeted therapies
  • Checkpoint inhibitors with cytotoxic chemotherapies
  • Discussion

CHAPTER 3:

  • Immune Agonists
  • Celldex Therapeutics' Varlilumab (CDX-1127)
  • OX40 agonists
  • MedImmune/AZ's OX40 agonist program
  • Roche/Genentech's OX40 agonist program
  • Nektar Therapeutics/BMS's NKTR-214, a CD122 agonist
  • Glucocorticoid-induced TNFR-related (GITR) protein agonist (Leap Therapeutics' TRX518)
  • Conclusions

CHAPTER 4:

  • Bispecific antibodies
  • Marketed bispecific antibody agents
  • Catumaxomab
  • Blinatumomab
  • Bispecific antibodies as an alternative to CAR-T cells
  • Xencor's cross-linking monoclonal antibody (XmAb) bispecific platform technology
  • Regeneron's native human immunoglobulin-format bsAb, REGN1979
  • Roche/Genentech's full-length bsAbs: Generated using CrossmAb technology
  • MacroGenics' MGD007: Generated using dual-affinity re-targeting (DART) technology
  • Conclusions

CHAPTER 5:

  • Therapeutic Anticancer Vaccines and Oncolytic viruses
  • Introduction
  • Cancer vaccines-a field rife with clinical failures
  • Why has the cancer vaccine field been so prone to clinical failure?
  • Marketed therapeutic cancer vaccines and oncolytic virus therapies
  • Dendreon/Valeant's sipuleucel-T
  • Amgen's talimogene laherparepvec (T-Vec)/Imlygic
  • Therapeutic cancer vaccines and oncolytic virus therapies in clinical development
  • Celldex's CDX-1401
  • Bavarian Nordic's PROSTVAC-VF
  • Argos Therapeutics' AGS-003
  • Sydys Corporation's CVac
  • Aduro Biotech's CRS-207
  • TapImmune's TPIV110 HER2/neu and TPIV200 folate receptor alpha multi-epitope vaccines
  • Genelux's GL-ONC1 oncolytic virus
  • Conclusions

CHAPTER 6:

  • Adoptive Immunotherapy for Cancer
  • Introduction
  • Adoptive immunotherapy with tumor infiltrating lymphocytes
  • 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
  • Successful targeting of KRAS G12D via adoptive immunotherapy in a case of metastatic colorectal cancer
  • Dr. Rosenberg's recent studies on neoantigen-reactive TILs for use in adoptive cellular immunotherapy
  • Commercializing TIL therapy
  • Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
  • Leading clinical programs in CAR T-cell based immunotherapy
  • Kite Pharma's KTE-C19 (axicabtagene ciloleucel)
  • Novartis' CTL019
  • Juno's JCAR015 and other Juno anti-CD19 CARs
  • Other CAR T-cell therapies that target hematologic malignancies
  • bluebird bio's bb2121 for multiple myeloma
  • CAR T-cell therapies that target solid tumors
  • Novartis/University of Pennsylvania's CARTmeso
  • EGFRvIII CAR T-cell therapies
  • Companies developing engineered improvements in CAR T-cell therapy
  • Bellicum Pharmaceuticals' technologies for modulation of CAR T-cell therapies
  • Cellectis' technologies for design and manufacture of “off-the shelf” CAR T-cell therapies
  • Manufacturing issues with CAR T-cell therapies
  • Can bispecific antibodies be competitive with CAR T-cell therapies?
  • Adptimmune recombinant TCR clinical candidates
  • Kite Pharma recombinant TCR program
  • Juno Therapeutics' recombinant TCR program
  • Recombinant TCR studies at the NCI
  • Conclusions
  • Market size estimates for the T-cell therapy market

CHAPTER 7:

  • General Conclusions
  • Major theme of this report: Immuno-oncology 2.0 or “second-wave” immuno-oncology
  • Approvals of checkpoint inhibitors
  • Biomarkers for checkpoint inhibitor treatments
  • Approved and clinical-stage immunotherapy biologics other than checkpoint inhibitors
  • Immunotherapy with TIL cells
  • Commercialization of TIL therapy
  • Adoptive immunotherapy with genetically engineered T cells bearing chimeric antigen receptors (CARs)
  • Manufacturing issues with CAR T-cell therapies
  • Adoptive immunotherapy via autologous recombinant TCR technology
  • General conclusions on the progress of cellular immunotherapy
  • Insight Pharma Reports survey on cancer immunotherapy
  • Outlook for cancer immunotherapy
  • References
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