Post on 01-Jun-2021
Cáncer de Vejiga – Cara a cara: • A favor de la Inmunooncología
Josep M Piulats
L Galluzzi et al. Oncotarget 5, 12472-12508 (2014)
L Galluzzi et al. Oncotarget 5, 12472-12508 (2014)
Anti-PD1 Anti-PDL1 Anti-CTLA4
L Galluzzi et al. Oncotarget 5, 12472-12508 (2014)
Anti-PD1 Anti-PDL1 Anti-CTLA4
Chemotherapy
Immunogenic Cell Death (ICD):
Immunogenic Cell Death (ICD):
Plasma membrane characteristics
Inflammatory cytokines released from dying cells
End-stage degradation products with pro-
inflammatory properties
TP53 activation and immunological consequences
O Kepp et al. Oncoimmunol 3, e955691 (2014)
O Kepp et al. Oncoimmunol 3, e955691 (2014)
Platinum salts as an ICD inductor:
SV Hato et al. Clin Cancer Res 20, 2831-2837 (2014)
Platinum salts as an ICD inductor:
SV Hato et al. Clin Cancer Res 20, 2831-2837 (2014)
Is bladder cancer an immunogenic disease?:
MS Lawrence et al. Nature 499, 214-218 (2013)
Is bladder cancer an immunogenic disease?:
A Snyder et al. NEJM 371, 2189-2199 (2014)
NA Rizvi et al. Science 348, 124-128 (2015)
JE Rosenberg et al. Lancet 387, 1909-19-20 (2016)
Is bladder cancer an immunogenic disease?:
Is bladder cancer an immunogenic disease?:
CY Ock et al. Clin Cancer Res 22, 2261-2270 (2016)
- Chemotherapy can be considered immunotherapy. - Bladder cancer has high rate of neoantigens. - Bladder cancer show a 30% of tumors with high CD8/PDL1.
What about clinical efficacy???
Atezolizumab:
JE Rosenberg et al. Lancet 387, 1909-19-20 (2016)
Pembrolizumab:
J Bellmunt et al. New Engl J Med 376, 1015-1026 (2017)
Pembrolizumab:
J Bellmunt et al. New Engl J Med 376, 1015-1026 (2017)
Something +
Synergy is the interaction of two or more agents or forces so their
combined effect is greater than the sum of their individual effects.
Sequential or Concomitant treatments.
DRUG A
DRUG B
DRUG A
DRUG B
Rational or Empirical combinations. Empirical combinations use one
drug that is standard treatment for that disease; Rational combinations try
to combine drugs with the objective to maximize any synergistic effect.
- Chemotherapy can be considered immunotherapy. - Bladder cancer has high rate of neoantigens. - Bladder cancer show a 30% of tumors with high CD8/PDL1.
What about clinical efficacy???
- Anti-PD1 antibodies are the standard of treatment in second line. - Rational combination with chemotherapy is being explored in
first line treatment.