Han Chong Toh

Han Chong Toh (National Cancer Centre Singapore, Singapore)
"Cellular Immunotherapy for Nasopharyngeal Cancer: Learning from the Past for a Better Tomorrow"


Tetrament of metastatic NPC with autologous dendritic cells transfigured with adenoviral veryor (AD5F35) expressing LMP1 and LMP2 genes in patients (NPC vaccine patient 004 -->  partial response; knowledge is of no value unless ups put it into practice Anton Chekhov).

Treatment of NOC with EPV using autologous T cell therapy
- phase II trial of GC+EBVST in advanced NPC
- Gemcitabine induces MDSCs
- T cells as living therapy (injet 10 T cells into the body can generate 3 logs T cells
- Demonstrated success in phase II solid tumor trials (Tessa’s phase II NPC trial showed improved IS rate and quality of lifet; response rate 43%
- Significant ling-term survival beyond 3 years (3-year, 37%, 4-yr 26%, 5-yr 11%)
- Strong response rate during uhmmunotherapy phass (complete response 6%, partial response 13%, response
- Spider plot of tumor sizes (Gem.carbiplatin and CTL therapy (N=20)



EBVST response to LMP2 is correlated with prolonged survival

Amalgamated serum cytokines analysis shows positive and negative correlated with survival (IFNG good, IL10, CCL20, VEGF, IL8 bad)

Chemo-rebound in monocytes MDSC sunset correlated with non-survival at years

Long-term survivors experience increased lymphoid by decreased

Theat the biomarker studies tell us

Phase III global NOC cTL trials: 220 patients from 5 countries and 30 hospital sites

Human gd T cells express multitude or receptors that canc be targeted for anti-tumor immunotherapy
(NKG2 receptor)


PIteintal

GdT cell s are capable of class I and II presentation
Battle of the antigen presenting cells (AOCs0

Generating Vg9Vd2 T cells with enhanced effector capabilities
MICA, MICB, and BTN3A1 are ligand of NGK

Vg9VCd2 T cells maintains enhanced cross presentation VS moDCs (IL2, IL2+


A clinical trial in Baylor [published in ASCO]
TGFb rich TME blunts anti-tumor immune response
-EBV specific CTLs with treasure dominant-negative TGFB recepotior (DNRII) can overcome TGF-b-mediated immune suppression in TME
-