108/03/08 癌症的細胞免疫療法

From Comfort CARE To Comfort CURE Cell Immunotherapy

從舒適照護 到舒適治療 Dr. Andrew YOUNG (M.D.) 楊友華 台灣細胞免疫醫學會

癌症治療的演進 ■ 手術治療 (?

~迄今) ■ 放射治療 (1890s~迄今) ■ 傳統化學治療 (1940s~迄今) ■ 精準治療 (1990s~迄今) ■ 細胞免疫治療 (1990s~迄今)

2

癌症治療⽅方法

化學療法 ⼿手術

放射線療法

免疫細胞療法

台灣細胞治療現況

➢ 細胞治療臨床試驗則有許多計畫執行中，34％為間質幹

細胞，19％為免疫細胞相關，為最大宗。 ➢ 但迄今， 台灣食品藥物管理署未核准過任何細胞治療產 Cell types (case number)

品。 Cell therapy

Gene therapy

Clinical Trial Number

16

1

12

2 8 4 0

15 1

8

3 2010

2011

12

16 9

9

2015

2016

7

4 2012

2013

2014

Year

2017

2018

TFDA 2010~2018/06/30

特管辦法開放細胞治療技術項目 ■ 項⽬目及適應症 ➢ ⾃自體使⽤用 ➢ 風險性低、安全性可確定

■ 採許可制 ➢ 醫療機構應擬訂計畫書向中 央主管機關申請許可 ➢ 操作實驗室應符合GTP相 關規範

項⽬目 適應症 ⾃自體CD34+ selection周邊⾎血幹細胞移植 " ⾎血液惡惡性腫瘤（hematological malignancies） • ⽩白⾎血病（不包括慢性骨髓⽩白⾎血病之慢性期） • 淋淋巴瘤 • 多發性骨髓瘤 " 慢性缺⾎血性腦中風 " 嚴重下肢缺⾎血症

⾃自體免疫細胞治療（包括CIK、NK、 " ⾎血液惡惡性腫瘤（hematological malignancies）經標準治療無效 DC、DC-CIK、TIL、gamma-delta T之 " 第⼀一⾄至第三期實體癌（solid tumor），經標準治療無效 adoptive T細胞輸入療法） " 實體癌第四期

⾃自體脂肪幹細胞移植

" 慢性或滿六週未癒合之困難傷⼝口 " 占總體表⾯面積百分之⼆二⼗十（含）以上之⼤大⾯面積燒傷或⽪皮膚創傷 受損 " ⽪皮下及軟組織缺損 " 退化性關節炎及膝關節軟骨缺損 " 其他表⾯面性微創技術之合併或輔助療法

⾃自體纖維⺟母細胞移植

" ⽪皮膚缺陷：皺紋、凹洞洞及疤痕之填補及修復 " ⽪皮下及軟組織缺損 " 其他表⾯面性微創技術之合併或輔助療法

⾃自體骨髓間質幹細胞（bone marrow mesenchymal stem cell）移植

" 退化性關節炎及膝關節軟骨缺損 " 慢性缺⾎血性腦中風 " 脊髓損傷

⾃自體軟骨細胞移植

膝關節軟骨缺損

➢ 核予⾄至多3年年效期，可申請 展延

■ 定期提報治療結果 ➢ 醫療機構應提報年年度施⾏行行結 果報告 ➢ 影響病⼈人權益與安全、不良 事件發⽣生數或嚴重度顯有異異 常者，得終⽌止施⾏行行

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2017 年年: US FDA 核准2項CAR-T 癌症免疫細胞治療元年年 1st

CAR-T

• August 30, 2017 FDA approval bring first gene therapy to the US; Kymriah (Novartis) $ 475,000

2nd CAR- • October 18, 2017 T FDA approves 2 CAR-T therapy 11.9 B Yescarta (Kite/Gilead) nd

$ 373,000

2018 年年諾⾙貝爾獎: 免疫治療已成為顯學 2017 年年銷售 額 12 億美⾦金金

Anti-CTLA-4 mAb

2017 年年銷售 額 49 億美⾦金金

Anti-PD-1 mAb

癌症免疫細胞治療: 下⼀一個黃⾦金金⼗十年年

醫療科技的第四根⽀支柱 ? 醫學⽀支柱演變 1. 藥品 2. ⽣生物製劑 3. 醫療設備 4.

?

細胞治療是醫療科技的第四根⽀支柱 Cell base therapeutics: The next pillar of medicine

醫學⽀支柱演變 1.

2.

3.

4.

藥品 ⽣生物製劑 醫療設備 細胞治療

癌症 疫苗

細胞 治療

⼿手術& 電療

癌 症 治 免疫 療 檢查點 抑制劑

化 療

⼩小分⼦子 標把 單株 抗體

傳統癌症治療⽅方式 Surgery ⼿手術切除 Chemotherapy 化學治療 Targeted

癌症

Therapy 標靶治療

Radiation

現有癌症治療⽅方式 有其限制及不⾜足!!

- 無法主動完全清除癌細胞 - 無法有效抑制癌症復發 - 強烈副作⽤用

Therapy 放射線治療

攻擊的療法 !

傳統癌症治療⽅方式 Surgery

現在多了了⼀一項

⼿手術切除

最新、最有效的抗癌⽅方式

Chemotherapy

彌補傳統治療⽅方式不⾜足

化學治療 Targeted

癌症

Therapy 標靶治療

免疫 細胞

Radiation Therapy 放射線治療

免疫細胞療法

•2011 Summit: Cell Therapy, Billion Dollar Global Business, Unlimited Potential, Chris Mason, PhD (University of London)

https://www.youtube.com/watch? v=MOLPhpRfYgU&list=PLoRln0Rmd31EjJ1_gu8BRpKeydVsunje7&in dex=6&t=0s

2011 Summit: Cell Therapy, Billion Dollar Global Business, Unlimited Potential, Chris Mason, PhD Chis Mason, PhD (University of London), presented the potential of the cell therapy industry to become a multibillion dollar industry as a result of R&D, investment and media coverage. Emphasizing the difference between cell therapy and regenerative medicine, he spoke about the need to distinguish the two fields and allow them to grow to their full potential. Mason touted cell therapies as potentially revolutionary solutions for unmet medical needs and called for an effective business model to bring these therapies to market.

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發展整合⼤大健康商業模式 (⽣生命的意義與企業的價值觀)

預防醫學

整合式醫療

治療後保健

⼤大數據收集 與統計分析 癌症AI程度診斷

癌症預防與治療

1.

舒適照顧+舒適治療+整合治療

2.

產業鏈（預防+檢查+技術+⽣生產+臨臨床+療後保健)!分⼯工、整 合、利利潤共享

3.

政府開放 !技術進來來、資⾦金金進來來、⼈人才進來來!產業成長、經 濟成長、走向國際

4.

⽣生命的意義在於!離苦得樂，健康的⼈人⽣生

What is Cell Therapy In fact it is not a new kind of therapy.

What about Blood Transfusion?

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10/21/16

Immunocell Therapy Treatment using LIVING CELLs Lymphocytes, Cytokines Induced Killer cells , CIK

分離周邊

周邊血單 擴增

Natural Killer Cell, NK Mesenchymal Stem Cell , MSC Dendritic Cell , DC Chimeric Antigen Receptorengineered T-Cell , CAR-T 回輸

擴增200倍

Cytokine-induced killer (CIK)cell •

CIK cells were first described by G.H. Schmidt-Wolf in 1991, who also performed the first clinical trial with CIK cells in the treatment of cancer patients in 1999.

•

They are generated by ex vivo incubation of human peripheral blood mononuclear cells (PBMC) or cord blood mononuclear cells with IFN-γ, anti-CD3 Ab, recombinant human IL-1 and recombinant human IL-2.

Yeh Ching Linn & Kam M. Hui Journal of Biomedicine and Biotechnology Volume 2010

•

These 45 clinical studies investigated 22 different tumor entities altogether enrolling 2,729 patients.

•

A mean response rate of 39 % and significantly increased OS, accompanied by an improved quality of life, were reported.

•

side effects of CIK cell treatment were minor. Mild fevers, chills, headache and fatigue were, however, seen regularly after CIK cell infusion.

•

CIK cells revealed numerous immunologic effects such as changes in T cell subsets, tumor markers, cytokine secretion and HBV viral load.

胃癌⼿手術後病患 只使⽤用化療 化療合併CIK療法

2年年存活率52.6% 2年年存活率73.5%

5年年存活率23.9% 5年年存活率40.4%

優

棍打愛⽝犬的治療經驗

Example of Treatment with SUFFERINGs 痛苦創傷的治療經驗 • T.B. 結核病 • Conventional CANCER TREATMENTS 傳統的主流癌 症療法 • D.M. , H/T (Life-long medication without curative effect) 糖尿尿病 ，⾼高⾎血壓⋯ （要終⽣生吃藥 但不能把疾病治癒）

Potential Risk Patient selection

Potential Risk C.R.S. Cytokine Storm Tumor Lysis Syndrome FLU Syndrome Fever Chillness Malaise

Possible caused by substances released during cellular lysis

Risk Prevention Good patient selection and assessment with skillful clinical communication and precaution.

Tumor burden?

Possible treatment respond?

Any possible indolent infection condition?

Excellent medial supportive treatment

Possible cause of Cytokine Storm 細胞素風暴暴的潛在風險 • Very heavy tumor burden with very good treatment effects (similar to tumor lysis syndrome, or a very severe blood transfusion reaction) 非常沈沈重的腫瘤負擔 遇到 非常 敏感的治療效果 • Severe asymptomatic infection state (Bateria, Virus, Fungus, Parasites ...) 嚴重的無症狀狀感染情況

Neoantigen

35M dx. Malignant LYMPHOMA, B-CELL Before tx. 2016/Aug/04 After tx. 2017/Apr/14

mNSCLC 3 CONSECUTIVE SUCCESSFUL CASES WITH DOUBLE LOCKING ERADICATION

TANG K.W. relevant tumor markers change during the treatment course DATE

CEA

CA125

CA199

CA153

2017DEC02

2.06

18.65

NIL

60.85

2018MAR02

1.47

6.45

13.59

6.99

2018APR24

1.17

5.46

10.05

5.3

Abnormal uptake lesions resolved just in 3-months treatment

Lung ca. with Diffuse Metastases 46 Female 2017/NOV/14,before tx.

2018/FEB/12 ,after one tx.course

2018JUNE01, 7 months after started tx.

Mr.HSU 57M ,relevant tumor markers change during treatment course without any cytotoxic chemotherapy CEA

NSE

CA125

2018JAN29

127.8

24.29

112

2018FEB05

94.7

14.26

114.6

2018FEB13

62.7

9.4

67.66

2018MAR16

10.82

11.76

16.96

2018APR16

5.55

14.21

14.06

2018APR25

5.37

14.24

12.03

2018MAY09

4.46

16

12.98

Mr. Cheung 56M dx. mNSCLC in JUNE/2017 Primary mass > 4cm T-CELL THERAPY + XALKORI Date

CEA tumor marker

MARCH

580

APRIL

300

MAY JUNE

180 126

Mr. Cheung 56M dx. mNSCLC in 
 JUNE/2017 Primary mass > 4cm 2017 JUNE ,befo re treatment

2018 MAY after 1st tx.

PET and CT image on the 
 same resolving tumor,
 2018/05/24

Clinical Oncology Specialty Helping Cancer Patient, 2018 by comment by Dr Andrew YOUNG

Surgical Oncology

Radiation Oncology

Medical Oncology

Immune Oncology

Knowing Cancer Entity

Not much +

Much ++

Very much ++++

Overwhelming +++++

Intervention

Very much ++++ Much ++++

Not much ++ Much +++

So much +++++ Not much +

Not enough + Very much +++++

+++

++

+++++

+

Contribution To Cancer Patient

Patient Suffering

Take Home Message • CIK immunotherapy can be new hope for all cancer patients.

• Strong Integrative Medicine will further consolidate the outcome of CIK immunotherapy.

• Both Quality and Quantity are paramount importance in CIK immunotherapy.

• NewLife Integrative Precision Medical Center can be your friendly partner.

承先啟後 繼往開來

Thank