Safety and antitumor activity of recombinant soluble Apo2 ligand

Avi Ashkenazi, Roger C. Pai, Sharon Fong, Susan Leung, David A. Lawrence et al.

Journal of Clinical Investigation • 1999

DOI PMC

Solid Tumor Treatment Study

behavioralmouseathymic

Objective: Evaluation of Apo2L (TRAIL) treatment on tumor cell apoptosis, progression suppression, and survival improvement in mice bearing solid tumors, including synergistic effects with chemotherapeutic drugs

Materials & Equipment Checklist

3 items

Gather these items before starting the experiment. Check off items as you prepare.

Materials3

Apo2L (Apo2 ligand/TRAIL)

Genentech Inc.

Amazon

5-fluorouracil

Amazon

CPT-11 (Irinotecan)

Amazon

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Protocol Steps

In vitro cytotoxicity screening

Tested Apo2L effects on 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer to determine cytostatic or cytotoxic effects

Note: Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines tested

View evidence from paper

“Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer”

Tumor xenograft establishment

Injected tumor cells into athymic mice to establish solid tumors

Note: Treatment with Apo2L was administered shortly after tumor xenograft injection

View evidence from paper

“Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence”

Apo2L treatment administration

Administered repeated intravenous injections of Apo2L to mice bearing solid tumors

Note: Repeated intravenous injections were used; treatment induced tumor cell apoptosis, suppressed tumor progression, and improved survival

View evidence from paper

“Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival”

Combination therapy with chemotherapeutic drugs

Treated mice with Apo2L in combination with 5-fluorouracil or CPT-11 to evaluate synergistic effects

Note: Combination treatment resulted in substantial tumor regression or complete tumor ablation

View evidence from paper

“Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation”

Toxicity assessment in nonhuman primates

Administered repeated intravenous injections of Apo2L in nonhuman primates to assess safety profile

Note: No detectable toxicity was observed to tissues and organs examined

View evidence from paper

“Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined”