SOLUBLE T-CELL ANTIGEN RECEPTORS - Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges - page 463

FIGURE 31.3 Effect of 264scTCR/IL-2 and ALT-801 on growth of subcutaneous human tumor
xenografts in nude mice. (A) A375 melanoma tumor cells (1 10 6 cells) were injected sub-
cutaneously into nude mice and tumors were allowed to grow to 200mm 3 . Starting on treatment
day 1, mice were administered 264scTCR/IL-2 (1.6mg/kg) or IL-2 (0.4mg/kg, molar equivalent
dose) for 4 days, followed by treatment every other day for a total of nine doses. (B) Subcutaneous
A375 tumor-bearing nude mice were treated i.v. with ALT-801 (1.6mg/kg, 0.5mg/kg, or 0.15mg/kg)
or IL-2 (0.4mg/kg or 0.12mg/kg) as described in (A). (C and D) Nude mice were injected s.c. with
p53 þ /HLA-A2.1 þ PANC1 (C) or p53 - /HLA-A2.1 - AsPC1 pancreatic tumor cells (D). Tumors were
allowed to establish to 25-100mm 3 and mice were treated with molar equivalent doses of IL-2 or
264scTCR/IL-2, or the dose equivalent volume of PBS as described in (A). (E) Subcutaneous
A375 tumor-bearing nude mice were treated i.v. with either 0.5mg/kg ALT-801, 0.5mg/kg control
TCR/IL-2 fusion (MART-1scTCR/IL-2) or PBS with four daily injections, followed by a 10-day rest
period and then four more daily injections. (F) Subcutaneous A375 tumor-bearing nude mice were
treated with 0.5mg/kg ALT-801 as described in (E) (dosing indicated by solid arrows) or with a 3.2-
fold higher molar equivalent amount per dose (0.4mg/kg) of IL-2 every 8 h for 5 days followed by a
10-day rest period and then every 8 h for five more daily doses (dosing indicated by dashed arrows).
For each study, tumor volumes (5-8 mice per group) were measured at least twice a week and were
plotted as mean SEM. Source: (A), (C), and (D) are reproduced with the publisher's permission
from Reference [17]. (E) is reproduced with the publisher's permission from Reference [23].

of 3.2-3.6 h in HLA-A2 transgenic mice, about twice that of
ALT-801 and 10-fold that of IL-2 [23]. Thus, these results
suggest that increasing the biological half-life of IL-2
without specific tumor binding, as is the case for the
MART1scTCR/IL-2 fusion,

activity than is seen with IL-2 alone in these models.
However, the combination of improved IL-2 serum half-
life and tumor recognition activity of the TCR domain
creates an even more potent antitumor agent as exemplified
by the ALT-801 fusion protein. leads to better antitumor