Dear valued clients and partners,

We have been experiencing a major coronavirus outbreak since this Chinese New Year holiday. With everyone’s efforts, WuXi Oncology & Immunology Unit (OIU) officially returned to work on February 12th . We thank you all for your continuous support and trust in WuXi OIU during this special period. Let us collaborate together, to do the right thing and do it right, and win back a fruitful 2020!

In the current issue of the OncoWuXi Newsletter, we would like to share with you our updates on genetically engineered Ba/F3 cell lines and corresponding in vivo / in vitro validation data . Other interesting topics covered in this issue include the updates on our integrated target identification and validation platform and FGFR targeted in vivo models.

OncoWuXi Newsletter will continue to keep you up-to-date with our recent progress in cancer research. As part of WuXi Research Service Division (RSD), our topnotch Oncology-Immunology team is dedicated to providing end-to-end services and solutions to support the ever-changing research needs of cancer and autoimmune diseases and is your ideal partner for enabling technological breakthrough and accelerating cancer drug discovery.
Translational Oncology
(1)    Engineered Ba/F3 cell lines with ALK mutations and validation data
  • Ba/F3-EML4-ALK
  • Ba/F3-EML4-ALK-L1196M
  • Ba/F3-EML4-ALK-C1156Y
  • Ba/F3-EML4-ALK-G1202R/L1196M
  • Ba/F3-EML4-ALK-G1202R
  • Validated with Crizotinib, Brigatinib, Lorlatinib, Alectinib, Ceritinib and Entrectinib in vitro or in vivo

(2)    Engineered Ba/F3 cell lines with EGFR mutations and validation data

(3)    Engineered Ba/F3 cell lines with TRK mutations and validation data
  • Ba/F3-ETV6-NTRK3-G623R
  • Ba/F3-ETV6-NTRK3-G696A
  • Ba/F3-ETV6-NTRK3-WT
  • Ba/F3-TPM3-NTRK1-G595R
  • Ba/F3-TPM3-NTRK1-G667C
  • Ba/F3-TPM3-NTRK1-WT
  • Ba/F3-LMNA-NTRK1-G595R
  • Ba/F3-LMNA-NTRK1-G667C
  • Validated with LOXO-101 and Entrectinib in vitro and on in vivo tumor model

CRISPR Platform
Integrated Target Identification and Validation Platform
(1)    Overview of target identification and validation platform

(2)    Generation of cell lines with inducible gene overexpression or knockdown via lentiviral system

(3)    Generation of cell lines with gene knockout or knockin via CRISPR-Cas9 system
  • Knockout via transient transfection, followed by 2D colony formation assay and drug response profiling
  • Knockout via lentiviral CRISPR/Cas9 system
  • Introduction of gene mutation or endogenous tagging by CRISPR/Cas9 knockin

(4)    In vitro CRISPR screen
  • Overview of in vitro CRISPR screen workflow
  • In-house pipeline for customized design
  • Cancer cell line based positive selection or negative selection screen to identify mechanism of drug resistance or essential genes
  • CRISPR screen in cancer cell and T cell co-culture to identify regulators of cancer cell response to T cell cytotoxicity
  • Bioinformatics workflow for screening data

(5)    In vivo CRISPR screen
  • Overview of in vivo CRISPR screen workflow
  • In vivo CRISPR screen for cancer immunotherapy modulators in syngeneic tumor models
  • Case study: in vivo CRISPR screen with a library derived from tumor evolution under immune selection identified a gene that is required for PD-1 independent T cell cytotoxicity

Targeted Oncology
FGFR Related In Vivo Models
(1)    Background of FGFR as drug target
  • FGFR biology
  • Summary of FGFR inhibitors and their in vitro activity

(2)    FGFR related CDX models
  • SNU-16 gastric cancer CDX model, validated with AZD4547, Dovitinib, LY2874455, TAS-120, BGJ398, and JNJ-42756493
  • Hep 3B and Huh-7 liver cancer CDX models, validated with BLU9931
  • RT112/84 bladder cancer, KMS-11 myeloma, and JHH-7 liver cancer CDX models

(3)    FGFR related PDX models
  • 11 PDX models with FGFR overexpression, covering NSCLC, GIST, and HCC cancer types
  • 7 PDX models with clinically relevant mutation or fusion
  • LU-01-0010 and LU-01-0048 NSCLC PDX models, validated with BKM120 and AZD4547

We sincerely appreciate your interest, time and support, and would like to hear your feedback so we can continuously improve our service. Please don't hesitate to email us if you have any questions, suggestions or concerns.

Best regards,
WuXi AppTec OncoWuXi Team