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Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

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Protect E.coli from Immune System K1:O16 capsule Idea from “bactoblood”, UCBerkeley, iGEM2007

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Page 1: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Taming Cancer by Inducing Immunity via E. coli

Presenter: Xu NanfangCai DanfengChen Yufei

Page 2: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

First, we need a E.coli that can escape the immune system after infusing into the blood

Page 3: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Protect E.coli fromImmune SystemK1:O16 capsule

Idea from “bactoblood”, UCBerkeley, iGEM2007

Page 4: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

polysialic acid is a frequent coating on mammalian cells, the human immune system does not recognize K1 as foreign

Together, these surface modifications allow the bacterium to avoid detection by the immune system and should extend the serum half-life to several hours rather than the less-than-5 minutes observed with rough strains

Both of these gene clusters have been installed into the genome of MC1061 in the course of preparing our chassis strain, MC828U

Page 5: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Amazing O2

First role of O2: to locate the cancer cells

Page 6: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Study shows that where there’s cancer existing, oxygen level is usually significantly lower than other parts of the body.

E. coli is anaerobic

Page 7: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Second role of O2: to act as a signal for the transcription of a series of factors.

Page 8: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

a

A

Density-sensing

Oxygen-sensing

Page 9: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

A

K1:O16

hydrolysis

inv

Page 10: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Petra Dersch and Ralph R.Isberg: A region of the Yersinia pseudotuberculosis invasinprotein enhances integrin-mediated uptake intomammalian cells and promotes self-association

Page 11: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Suicidal Component

Make sure that E.coli kills oneself after several generations of division

Page 12: Taming Cancer by Inducing Immunity via E. coli Presenter: Xu Nanfang Cai Danfeng Chen Yufei

Advantages:

1. Dependent on the immune system of oneself

2. Detect cancer at an early stage

3. Cancer-specific

Problems:

1. The efficiency of eliminating capsules

2. In vivo vs. in vitro