6. 癌細胞會被標記特殊抗原和一般正常細胞區分
Murphy K, Travers P, Walport M, eds. Janeway's Immunobiology. 7th ed. Garland Science,
Taylor & Frances Group, LLC. New York, NY: 2008.
6
7. Murphy K, Travers P, Walport M, eds. Janeway's Immunobiology. 7th ed. Garland Science,
Taylor & Frances Group, LLC. New York, NY: 2008.
7
8. Murphy K, Travers P, Walport M, eds. Janeway's
Immunobiology. 7th ed. Garland Science, Taylor & Frances
Group, LLC. New York, NY: 2008.
8
9. Namm JP, Li Q, Lao X, et al. J Surg Oncol. 2012;105:431-435.
9
10. Namm JP, Li Q, Lao X, et al. J Surg Oncol. 2012;105:431-435.
B細胞被活化產生抗體去和癌細
胞抗原對抗
10
11. Namm JP, Li Q, Lao X, et al. J Surg Oncol. 2012;105:431-435.
T細胞會去辨識癌細胞上的抗原，並
加以摧毀癌細胞
11
12. Namm JP, Li Q, Lao X, et al. J Surg Oncol. 2012;105:431-435.
12
13. Cancers inhibit the normal immune response through a variety of
mechanisms, enabling malignant cells to grow and spread.
Ribas A, Butterfield LH, Glaspy JA, Economou JS. J Clin Oncol. 2003;21:2415-2432.
Kasiske BL, Wang C, et al. Am J Transplant. 2004;4(6):905-913.
Le Mire L, Wojnarowska F, et al. Br J Dermatol. 2006;154(3):472-477.
Herrero JI. Liver Transpl. 2009;15(suppl 2):S90-S94.
Abbas AK, Lichtman AH. Basic Immunology. 3rd ed. 2011.
Dunn GP, et al. Nat Rev Immunol. 2006;6(11):836-848.
13
17. BCG, Bacille Calmette-Guerin; mABs, monoclonal antibodies; CA, cancer; IFN-α, interferon alpha; IL-2, interleukin-2
1. Kirkwood JM, Ferrone S, et al. CA Cancer J Clin. 2012;62(5):309-335.
2. Lesterhuis WJ, Punt CJ, et al. Nat Rev Drug Discov. 2011;10(8):591-600.
熱血時期 疑慮階段 復興時期
1978-1985 1985-1997 1997-
1973 Discovery
of the
dendritic cell
(Steinman)
1976
1st study
with BCG in
bladder CA
1978
Discovery of
tumor
specific
mABs
1985
1st study with
adoptive T-cell
transfer in CA
1990s
Discovery of
role of
checkpoint
inhibitors
in CA
1986
IFN-α
(cytokine)
approved for
CA
1992
IL-2 (cytokine)
approved
for CA
1997
1st mAB
approved
for CA
2010
1st cellular
immunotherapy
approved for CA
2011
1st checkpoint
inhibitor
approved
for CA
1890s
1st CA vaccine
developed
(Coley)
Adapted with permission from Lesterhuis WJ, et al2 and Kirkwood JM, et al. J Clin Oncol. 2008;26(20):3445-3455.
3. Krummel MF, Allison JP. J Exp Med. 1995;182(2):459-465.
4. Lotze M. In: Cancer: Principles & Practice of Oncology. 9th ed. 2011.
5. Leget GA, Czuczman MS. Curr Opin Oncol. 1998;10(6):548-551.
說歷史
17
18. 說歷史
• 1796年，當時Edward Jenner生產了第一種用牛
痘免疫接種預防天花的疫苗。
• Paul Ehrlich的研究產生了“magic bullet”的概
念，使用抗體專門針對疾病。用於治療用途的
純種單株抗體，於1975年開始生產。
• Rosenberg導入了癌症的免疫細胞療法。 在20
世紀80年代後期，他們報導了1205例轉移性癌
症患者，接受不同類型活性特異性免疫治療，
發現有不顯著的腫瘤消退比率（2.6-3.3％）。
Rosenberg SA. Adoptive immunotherapy of cancer: accomplishments and prospects. Cancer Treat Rep. 1984; 68 (1): 233–55.
18
19. 說歷史
• 進入分子醫學時代，解析抗體結構與其多樣性的
基因重組原理，開啟製造單株抗體和標靶治療。
• 1980s- 1990s, 細胞激素開始用於癌症治療:
interferon, interleukin…
• 1997年，第一種抗癌治療藥物Rituximab單株抗體
被FDA批准用於治療濾泡性淋巴瘤。後續陸續有10
多種單中抗體研發、上市。
1. Yang Q, Hokland ME, Bryant JL, Zhang Y, Nannmark U, Watkins SC, Goldfarb RH, Herberman RB, Basse PH. Tumor-localization by adoptively
transferred, interleukin-2-activated NK cells leads to destruction of well-established lung metastases. Int. J. Cancer. 2003; 105 (4): 512–9.
2. Egawa K . Immuno-cell therapy of cancer in Japan. Anticancer Res. 2004; 24 (5C): 3321–6.
3. Li K, Li CK, Chuen CK, Tsang KS, Fok TF, James AE, Lee SM, Shing MM, Chik KW, Yuen PM Preclinical ex vivo expansion of G-CSF-mobilized
peripheral blood stem cells: effects of serum-free media, cytokine combinations and chemotherapy. Eur. J. Haematol. 2005; 74 (2): 128–35.
19
43. Regenerative Medicines Market: Global Opportunity
Analysis and Industry Forecast, 2015–2022. Allied Market
Research: Pune,Maharashtra, India: August 2016;
43
70. Regenerative Medicines Market: Global Opportunity
Analysis and Industry Forecast, 2015–2022. Allied Market
Research: Pune,Maharashtra, India: August 2016;
9
88. 處置
• 在免疫治療期間，應密切監測病人是否發
生免疫相關不良反應，並依據「美國國家
癌症研究機構（National Cancer Institute,
NCI）」的最新版「常見不良事件評價標準
（Common Terminology Criteria for Adverse
Events, CTCAE）」進行不良反應程度分級，
最後依據級別進行處置。
27
Management of immune-related adverse events in patients treated with immune
checkpoint inhibitor therapy: American society of clinical oncology clinical practice
guideline. Journal of Clinical Oncology, JCO2017776385.
93. Case 1
• A 54-year-old man with advanced melanoma received a trial
of anti-PD-1 treatment with pembrolizumab combined with
radiotherapy. After 4-cycles of anti-PD-1 treatment, the
findings significantly progressed and air-bronchograms at
right lower lobe with obstructive pneumonitis was found.
32
Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports. Medicine (Baltimore). 2017;96(1):e5747.
94. Case 2
• A 57-year-old man with invasive thymoma received
photodynamic therapy (PDT) for pulmonary, pleural lesions
and followed by the self-paid concurrent treatment with
ipilimumab and nivolumab every 3 weeks. Three months later,
the findings significantly progressed and involved all lobes,
with decreased lung volumes and pleural effusion.
33
Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports. Medicine (Baltimore). 2017;96(1):e5747.
95. Case 3
• A 79-year-old man with advanced proximal jejunal cancer
underwent primary lesions resection and received proton
therapy over pulmonary metastatic lesions, followed by the
self-paid anti-PD-1 treatment. After 4-cycles of treatment, the
findings showed multilobular opacities over both lower lungs.
34
Pneumonitis in cancer patients receiving anti-PD-1 and radiotherapies: Three case reports. Medicine (Baltimore). 2017;96(1):e5747.
96. Case 4
• A 98-year-old man with advanced
UC of bladder, disease recurrence
with lung metastases, received
anti-PD-1 treatment every 3
weeks. One month later after 5
cycles of treatment , hair color
change(blue-green color) was
found.
35Hair Repigmentation During Immunotherapy Treatment With an Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1
Agent for Lung Cancer. JAMA Dermatol. 2017 Nov 1;153(11):1162-1165.
97. Case 5
• A 67-y/o man with small cell lung cancer, extensive stage, failure of
1st line chemotherapy of PVP and 2nd line chemotherapy of
TOPOTECAN, with liver metastases, underwent anti-PD-1 treatment
every 2 weeks. One week after 1st cycle treatment, weakness of all
limbs were developed. The problem was worse gradually.
• MRI of brain and T-L spine: No obvious lesion.
• CSF study:
– WBC 2/uL, RBC 2/uL, Lymphocyte 50/uL, Neutrophil 50/uL,
Eosinophil 0
– Glucose-CSF 119mg/dl (blood sugar: 141mg/dl); Total protein-
CSF 65mg/dl (blood t. protein: 5.2g/L; T. protein-CSF normal
range: 15-45mg/dl ); LDH-CSF 18U
36
98. Case 5
• NCV: Motor conduction study showed reduced CMAP amp, slowed NCV,
delayed distal latencies, prolong F latencies over right median, bil ulnar n
and no response of left median n. Sensory conduction study of right
median, left ulnar and radial nerves disclosed reduced SNAP amp, delayed
onset latency. No response of left median n and right ulnar n.
37
治療前，多發肝轉移
，脾臟轉移!
2個月後，肝轉移消
失，脾臟病灶縮小!
