biotecnologia no combate ao câncer - ufrj - início · para combate ao câncer ... terapia celular...
TRANSCRIPT
![Page 1: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/1.jpg)
Biotecnologia no
combate ao câncer
Martin Bonamino
I SBERJ – 09-2013
![Page 2: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/2.jpg)
Microambiente tumoral
![Page 3: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/3.jpg)
Biotecnologia como abordagem
para combate ao câncer
• Bloqueio de fatores estimuladores
• Anticorpos Monoclonais específicos para o tumor
• Anticorpos Monoclonais imuno-moduladores
• Terapia celular/gênica
![Page 4: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/4.jpg)
Scott et al, Nat Rev Cancer 2012
![Page 5: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/5.jpg)
Weidle et al, Cancer Gen Proteom 2013
mAbs: estruturas e alternativas
![Page 6: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/6.jpg)
Anticorpos Monoclonais: tumor como alvo
![Page 7: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/7.jpg)
Rituximab – mAb quimérico anti CD20 - IgG
![Page 8: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/8.jpg)
Rituximab – mAb quimérico anti CD20 - IgG
![Page 9: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/9.jpg)
Cetuximab – mAb quimérico anti EGFR – IgG1
Panitumumab – mAb humanizado anti EGFR – IgG2
![Page 10: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/10.jpg)
![Page 11: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/11.jpg)
Scott et al, Nat Rev Cancer 2012
![Page 12: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/12.jpg)
Scott et al, Nat Rev Cancer 2012
![Page 13: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/13.jpg)
Anticorpos Monoclonais: sistema imune como alvo
![Page 14: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/14.jpg)
![Page 15: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/15.jpg)
![Page 16: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/16.jpg)
Bloqueio de CTLA-4
![Page 17: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/17.jpg)
Adapted from ASCO 2008 meeting. Suzanne Louise Topalian, MD
![Page 18: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/18.jpg)
T Cell Activation by TCR and
Co-stimulation Through CD28
Dendritic
cell T cell
MHC
B7
TCR
CD28
Antigen
CTLA4
![Page 19: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/19.jpg)
CTLA4 Receptors Are Up-Regulated Following
T-Cell Activation
Dendritic
cell T cell
MHC
B7
TCR
CD28
Antigen
CTLA4
![Page 20: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/20.jpg)
Dendritic
cell T cell
MHC
B7
TCR
CD28
Antigen
CTLA4
CTLA4 Negatively Modulates
T-Cell Activation
![Page 21: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/21.jpg)
Dendritic
cell T cell
MHC
B7
TCR
CD28
Antigen
CTLA4
Blocking Antibodies to CTLA4 Allow Positive
Signaling from Costimulatory Molecules to T Cells
Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996;271:1734-1736.
![Page 22: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/22.jpg)
![Page 23: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/23.jpg)
![Page 24: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/24.jpg)
Survival Rate Ipi + gp100 N=403 Ipi + pbo
N=137 gp100 + pbo
N=136
1 year 44% 46% 25%
2 year 22% 24% 14%
Ipilimumab Improves Overall Survival
compared to control
Ipi + gp100 (A)
Ipi alone (B)
gp100 alone (C)
1 2 3 4 Years
![Page 25: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/25.jpg)
What mediates anti-CTLA4-induced durable tumor regressions?
Brown:
CD8+ T
cells
Blue:
melanoma 2005 Durable
response
> 5 years
Treatment with anti-CTLA4
antibodies
The great majority of responses last years without relapses:
- Longest responder: Ongoing since May 2001
- Response rate: ~10%
![Page 26: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/26.jpg)
Metastatic Melanoma Response to Ipilimumab
Before Ipilimumab
04/22/11
After Ipilimumab
08/05/11
![Page 27: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/27.jpg)
Years
Immunotherapy
Pe
rce
nt
ali
ve
1 2 3 0
Targeted therapy
Pe
rce
nt
ali
ve
1 2 3 0 Years
Immunotherapy vs targeted therapy for melanoma
![Page 28: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/28.jpg)
Bloqueio de PD1
![Page 29: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/29.jpg)
Células tumorais são capazes de matar
linfócitos efetores infiltrantes
http://www.bmsimmunooncology.com/tumor-immunosuppression.aspx
![Page 30: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/30.jpg)
Expressão de PD-1L por células tumorais
Marcação periférica Marcação difusa
HPV-Associated Head and Neck Squamous Cell Carcinoma
Lyford-Pike et al. CanRes 2013
![Page 31: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/31.jpg)
Enhancing Immune Responsiveness
PD1 Ab (MDX1106)
Phase I, single dose,
Tolerable, responses in
Colon, Lung, MM, RCC
Brahmer, ASCO 2008
PDL1 Ab
Phase I trial ongoing
PD1 Ab Phase 1,
multi dose, tolerable,
PRs in RCC, MM and
Lung, Sznol, ASCO 2010
![Page 32: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/32.jpg)
Durable partial regression of metastatic
kidney cancer following 3 doses of
anti-PD-1 (10 mg/kg)
01/15/08, pre-Rx 07/22/08 04/22/08
72 year old male with RCC metastatic to lung, LN, muscle,
bone, pancreas. Prior therapies included HDAC inhibitor,
sunitinib, and sorafenib.
Brahmer et al., JCO 2010
![Page 33: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/33.jpg)
33
Percent Change in Tumor Burden in RCC Patients
*Patients treated with the 10 mg/kg dose †Upper horizontal line denotes no change; lower horizontal line denotes 30%
decrease (RECIST threshold for PR).
Abbreviations: PR = partial response; RCC = renal cell carcinoma; RECIST = Response Evaluation Criteria in Solid Tumors
![Page 34: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/34.jpg)
Outros alvos de intervenção
Kwek et al, Nat Rev Cancer 2012
![Page 35: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/35.jpg)
Anticorpos Bi-específicos
![Page 36: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/36.jpg)
Frankel and Baeuerle, Curr Opin Chem Biol 2013
![Page 37: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/37.jpg)
IL-2
IFN
IL-15
IL-21
Peptide vaccine
DC vaccine
Genetic vaccine
OX40
CD137
CD40
PD1 CTLA4
T cell cloning TCR or CAR
genetic engineering
![Page 38: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/38.jpg)
Terapia celular
![Page 39: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/39.jpg)
39
Tumor Infiltrating Lymphocytes
![Page 40: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/40.jpg)
Immunotherapy
![Page 41: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/41.jpg)
Rosenberg and Dudley, Curr Opin Immunol 2009
![Page 42: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/42.jpg)
Rosenberg and Dudley, Curr Opin Immunol 2009
![Page 43: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/43.jpg)
ACT: Transferência adotiva de células
NMA: Não Mieloablativo
![Page 44: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/44.jpg)
Terapia gênica
![Page 45: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/45.jpg)
Transferência gênica de TCR
![Page 46: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/46.jpg)
![Page 47: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/47.jpg)
Receptores Quiméricos de Antígenos (CARs)
![Page 48: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/48.jpg)
Redirecting lymphocyte specificity for tumor elimination
![Page 49: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/49.jpg)
Chimeric Antigen Receptor (CAR)
Adapted from Pule et al, 2003
MHC-independent antigen
recognition;
High affinity for the antigen;
Independent of patient-
derived TILs
![Page 50: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/50.jpg)
Multiple signals required
T lymphocyte activation
![Page 51: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/51.jpg)
Acuto et al., 2003
Chimeric Antigen Receptor (CAR)
![Page 52: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/52.jpg)
1st generation
2nd generation
3rd generation
Chimeric Antigen Receptor (CAR)
![Page 53: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/53.jpg)
Clinical trials – 1st generation CAR
Nature Medicine, 2008
![Page 54: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/54.jpg)
Sadelain et al, Cancer Disc 2013
![Page 55: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/55.jpg)
Kochenderfer et al, Blood 2010
NHL – B cells
CAR 19-28z
Clinical trials - 2nd generation CAR
![Page 56: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/56.jpg)
Porter DL, et al. N Engl J Med 2011 Kalos M, et al. Sci Transl Med 2011
CLL-B
CAR 19-BBz
Clinical trials - 2nd generation CAR
10e7 cels
![Page 57: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/57.jpg)
Grupp, et al. N Engl J Med 2013
![Page 58: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/58.jpg)
Sleeping Beauty Transposon
Chicaybam et al, 2013
![Page 59: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/59.jpg)
Sleeping Beauty Transposon
Chicaybam et al, 2013
![Page 60: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/60.jpg)
Strategies to circumvent adverse effects
Chicaybam et al, 2011
a)
b) d)
c)
![Page 61: Biotecnologia no combate ao câncer - UFRJ - Início · para combate ao câncer ... Terapia celular . 39 Tumor Infiltrating Lymphocytes . Immunotherapy . Rosenberg and Dudley,](https://reader033.vdocuments.com.br/reader033/viewer/2022052922/5c1541e509d3f2256b8d0e70/html5/thumbnails/61.jpg)
Challenges and Solutions in Cancer Research and Treatment Club Med Mangaratiba, Rio de Janeiro, Brazil April 27-30, 2014