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癌症免疫疗法:从早期成功促进临床结果改善

Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes

出版商 Insight Pharma Reports 商品编码 504305
出版日期 内容资讯 英文 218 Pages
商品交期: 最快1-2个工作天内
价格
癌症免疫疗法:从早期成功促进临床结果改善 Cancer Immunotherapy: Building on Initial Successes to Improve Clinical Outcomes
出版日期: 2017年04月30日内容资讯: 英文 218 Pages
简介

本报告研究癌症免疫治疗药开发趋势,汇整免疫检查点抑制剂、癌症疫苗、T细胞输入疗法等主要药剂之开发和核准、上市情况、主要产品概要、主要企业行动、未来展望等。

摘要整理

第1章

  • 前言
  • 癌症免疫疗法早期历史:Coley毒素
  • 免疫调整药的细胞介质
  • 介白素-2
  • α干扰素
  • 介白素-12
  • 先天性免疫及适应免疫间桥梁的介白素-12
  • 作为抗癌剂的介白素-12调查
  • 介白素-10
  • 介白素-15
  • Admune/Novartis的heterodimeric IL-15:IL-15Rα (hetIL-15)
  • Altor的ALT-803
  • 结论:细胞介质为基础之癌症免疫治疗药

第2章

  • 何为免疫检查点?
  • CTLA-4堵剂
  • Ipilimumab
  • Tremelimumab
  • PD-1堵剂
  • Nivolumab
  • 黑色素瘤的nivolumab+ipilimumab合并疗法
  • Pembrolizumab
  • 作为晚期NSCLC的第一选择药物的Pembrolizumab
  • 误配修补欠损大肠癌的Pembrolizumab
  • 合并免疫治疗的Pembrolizumab研究
  • PDR001
  • PD-L1堵剂
  • Atezolizumab
  • 泌尿上皮癌治疗的Atezolizumab
  • NSCLC治疗的Atezolizumab
  • 其他固态肿瘤治疗的Atezolizumab
  • 其他抗PD-L1 mAb剂
  • Durvalumab
  • Avelumab
  • 抗LAG-3剂
  • 抗TIM-3
  • NewLink Genetics:小分子IDO路径抑制剂及检查点抑制剂
  • Infinity:肿瘤免疫抑制调整之PI3Kγ抑制剂IPI-549
  • 检查点抑制剂治疗的生物标记
  • 标靶生物标记
  • 基因生物标记
  • 免疫生物标记
  • 治疗中透过检查点抑制剂的生物标记测试使用
  • 检查点抑制剂+放射治疗
  • 检查点抑制剂+标靶治疗
  • 检查点抑制剂+细胞毒性化学疗法
  • 讨论

第3章

  • 免疫致效剂
  • Celldex Therapeutics的Varlilumab (CDX-1127)
  • OX40致效剂
  • MedImmune/AZ的OX40致效剂程序
  • Roche/Genentech的OX40致效剂程序
  • Nektar Therapeutics/BMS的NKTR-214, CD122致效剂
  • 糖皮质素诱发的TNFR相关 (GITR) 蛋白质致效剂 (Leap Therapeutics?TRX518)
  • 结论

第4章

  • 双特异性抗体
  • 上市双特异性抗体制剂
  • Catumaxomab
  • Blinatumomab
  • 作为替代CAR-T细胞的双特异性抗体
  • Xencor:交联单株抗体 (XmAb) 双特异性平台技术
  • Regeneron:天然人类免疫球蛋白格式bsAb, REGN1979
  • Roche/Genentech
  • MacroGenic的MGD007
  • 结论、其他

第5章

  • 抗癌疫苗和溶瘤病毒
  • 前言
  • 癌症疫苗:充斥临床失败案例的领域
  • 上市癌症疫苗和溶瘤病毒疗法
  • Dendreon/Valeant:sipuleucel-T
  • Amgen:talimogene laherparepvec (T-Vec)/Imlygic
  • 临床开发中的癌症疫苗和溶瘤病毒疗法
  • Celldex:CDX-1401
  • Bavarian Nordic:PROSTVAC-VF
  • Argos Therapeutics:AGS-003
  • Sydys Corporation:CVac
  • Aduro Biotech:CRS-207
  • TapImmune:TPIV110 HER2/neu□TPIV200叶酸受体alpha multi-epitope疫苗
  • Genelux的GL-ONC1溶瘤病毒
  • 结论、其他

第6章

  • 癌症的输入免疫疗法
  • 前言
  • 肿瘤浸润淋巴球和输入免疫疗法
  • 上皮癌中基于突变特异的CD4+ T细胞的输入免疫疗法
  • TIL疗法商业化
  • CAR T细胞基础之免疫疗法主要临床程序
  • Kite Pharma:KTE-C19 (axicabtagene ciloleucel)
  • Novartis:CTL019
  • Juno:JCAR015□其他的抗CD19 CAR
  • 血液恶性肿瘤为标靶的其他CAR T细胞疗法
  • bluebird bio:多发性骨髓瘤的bb2121
  • 固态肿瘤为标靶之CAR T细胞疗法
  • Novartis/University of Pennsylvania:CARTmeso
  • EGFRvIII CAR T细胞疗法
  • Bellicum Pharmaceuticals:CAR T细胞疗法的调整技术
  • Cellectis:「off-the shelf」CAR T细胞治疗药的设计和制造技术
  • CAR T细胞疗法制造课题
  • Adptimmune:基因重组TCR临床候补
  • Kite Pharma:基因重组TCR程序
  • Juno Therapeutics:基因重组TCR程序
  • NCI的基因重组TCR研究
  • 结论
  • T细胞疗法市场规模推估、其他

第7章

  • 结论
  • 本报告主要议题:免疫肿瘤学2.0 (或是第二波免疫肿瘤学)
  • 检查点抑制剂的核准
  • 检查点抑制剂的生物标记
  • 已核准及临床阶段之免疫生物制剂 (检查点抑制剂以外)
  • TIL细胞的免疫疗法
  • TIL疗法的商业化
  • CAR T细胞疗法制造课题
  • 透过自体基因重组TCR技术的输入免疫疗法
  • 细胞免疫疗法进步:一般性结论
  • 癌症免疫疗法展望
  • 参考资料、其他
目录

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