Biomedical Engineering Reference
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FIGURE 31.5 Antitumor activity of 264scTCR/IgG1 and ALT-802 in xenograft tumor models.
(A) Female athymic nude mice were injected i.v. with p53 þ HLA-A 0201 þ A375-C15N human
melanoma tumor cells and treated with PBS, 30mg/kg anti-STX2 mAb (irrelevant IgG1 isotype
control), or 264scTCR/IgG1 at doses ranging from 0.1 to 30mg/kg as described previously [14].
Forty-two days after tumor cell injection, the lungs were removed, lung nodules were counted, and
the mean number of lung nodules ( SEM) was plotted. Source: (A) is reproduced with publisher's
permission from Reference 14 (B) Nude mice were injected i.v. with p53 þ HLA-A 0201 þ A549-A2
human nonsmall cell lung tumor cells on study day 0. The tumor-bearing mice were treated i.v. on
study days 10, 13, 17, 20, 24, 27, and 33 with 3mg/kg ALT-802 or ALT-802LALA or an equivalent
volume of PBS. Thirty-four days after tumor cell injection, the lungs were removed, lung nodules
were counted, and the mean number of lung nodules ( SEM) was plotted. (C) Nude mice bearing
subcutaneous p53 þ HLA-A 0201 þ human melanoma A375-C15N tumor cells were treated with
PBS, cisplatin, ALT-802, or cisplatin þ ALT-802 as indicated in the figure legend. Tumor volumes
were measured every other day and means SEM were plotted.
treated i.v. with up to eight doses at 10mg/kg ALT-802
over a 4-week period did not exhibit any clinical signs
of toxicity. Pharmacokinetic analysis has also been con-
ducted indicating that ALT-802 has a half-life of
31.4.4 Evaluation of Combination p53-Specific STAR
Fusion Protein and Chemotherapy Regimens in Tumor
Efficacy Models
38 h in
transgenic HLA-A 0201 mice and 28 h in cynomolgus
monkeys, which is similar to that of other IgG fusion
proteins (J. Egan, unpublished data). Together these results
indicate that ALT-802 exhibits potent Fc-mediated anti-
tumor activity against lung tumors in our experimental
metastatic model with potential use as a cancer therapeutic
in humans.
Through development of novel cancer therapies over the
past 20 years, it is apparent that combination regimens,
including biological and chemotherapeutic agents, provide
more effective outcomes than respective monotherapies
[47,48]. These effects may be result from one agent
sensitizing the tumor cells to the cytotoxic activity of
another agent. For example, antibody-based approaches
have been shown to be active in targeting tumor antigens
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