Related U.S. Application Data 5 страница

FIG. 12F

CD
< 0
T“

Q О

FIG. 12G

CD169

< .

F4/80

а

-о

atent Jan. 10, 2017 Sheet 21 of 53                                      US 9, 539, 210 В

CD169

B220

+CLL

spleen

■

GO
m

■

GJ

>

CD11c                     LYVE-1                CD169

B220                       B220                    B220

popliteal lymph node

U. S. Patent Jan. 10, 2017 Sheet 22 of 53                                    US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 23 of 53

US 9, 539, 210 B2

FIG. 13B

Subset f

I^B-CLL □ +CLL

CD169⁺Mph CD11c^hi3hcDC

CD169⁺

CD11c^hi9h

FIG. 13C

PNAd Gr-1 CD8                                       CD4                B220

FIG. 13D

U. S. Patent Jan. 10, 2017 Sheet 24 of 53                                    US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 25 of 53

US 9, 539, 210 B2

FIG. 14A

Adv

В cells

FIG. 14D LYVE-1 B220

endothelial

cells

Lumen

Macrophage Sinus lining cell SCS floor

FIG. 14B

d

VSV                     Fluospheres                     Merge

FIG. 14E

atent Jan. 10, 2017 Sheet 26 of 53                                      US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 27 of 53

US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 28 of 53

US 9, 539, 210 B2

В cells                    CD169

SCS floor

FIG. 16C

FIG. 16E

FIG. 16D

U. S. Patent Jan. 10, 2017 Sheet 29 of 53                                    US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 30 of 53

US 9, 539, 210 B2

V110YEN В cells WT В cells

FIG. 17B

О            10           20            30

Time [min]

U. S. Patent Jan. 10, 2017 Sheet 31 of 53                                    US 9, 539, 210 B2

FIG. 17D

i

i

/
/-
/
/

⁷ 50-

r

I

I

r- 0.

superficial follicle

**

30 min UV-VSV-IND

no virus

30 min UV-VSV-NJ

FIG. 17E

U. S. Patent Jan. 10, 2017 Sheet 32 of 53                                    US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 33 of 53

US 9, 539, 210 B2

FIG. 18B

WT                               VI10YEN

FIG. 18A

10° ________ 10²₁₀° 10²

VSV-IND-Alexa488

10° -------------- ► 10²₁₀° 10²

VSV-NJ-Alexa488

Flou: KoJc

Time (s)

VSV-NJ

*. *i

MOI = 1000

■ *

FIG. 18C

VSV-IND-Alexa568

MOI = 1000 ¹

U. S. Patent Jan. 10, 2017 Sheet 34 of 53                                    US 9, 539, 210 B2

U. S. Patent

Jan. 10, 2017

Sheet 35 of 53

US 9, 539, 210 B2

О

*

о

_□

LL

Neutralizing titler (Iog2)

■ UV-VSV-Alexa488

□ uv-vsv

lgMday4 IgGdaylO

FIG. 18D

Diluted VSV

MOI = 005

(1x10¹)

VSV Supernatant

MOI = 0. 0005

(1x10¹)

10°_ „_т„„_|„,. _|„„, _|„, у₁₁. _т1. ₁. _1|j,... |,        , || |. | I | _t

Time (s)

-------- ►

MOI = 0. 0005

(1x10¹)

I I I *! " |l I I ГI I I 1¹¹ГГ'ГТТ 50

FIG. 18E

U. S. Patent

Jan. 10, 2017

Sheet 36 of 53

US 9, 539, 210 B2

Adherent cells                                          Adherent cells                                               Adherent cells

(% of input)                                              (% of input)                                                    (% of input)

FIG. 19A

FIG. 19B

V110YEN В cells

WT В cells

FIG. 19E

U. S. Patent Jan. 10, 2017

Sheet 37 of 53

US 9, 539, 210 B2

Cd 169

B220

ICAM -1                          ICAM -1

FIG. 19C

Cd 169

B220

VCAM -1                   VCAM - 1

FIG. 19D

' — о

Л            ГЧ1

о

VSV-IND MHC-II

ш > - о

§ Q

FIG. 20A

U. S. Patent

Jan. 10, 2017

Sheet 38 of 53

US 9, 539, 210 B2

w

Ф о

co

Ш

> о

E E

•••

••

200 -

•i

>

tn о tn

.... •••• •••.

••••

•»

i

t ——*i

о

< D
s:

100 -

i

• «

s

ф о c ns

E о

ч

ИГ

»

t.

< /)

0 4

t

Q

В cells with VSV

В cells w/o VSV

FIG. 20B

Time (min after UV-VSV)

U. S. Patent

Jan. 10, 2017

Sheet 39 of 53

US 9, 539, 210 B2

VI10YEN В

VSV-IND488

В220

+CLL

FIG. 20G

В cell frequency

Follicular (%)                    T/B border (%)

V110 YEN

FIG. 20H

4*       ■ ■ ‘Л ■ ■

WT VI10YEN WT VI10YEN

Deep follicle Superf. Follicle & SCS

Deep follicle

Superf. Follicle
& SCS

Deep follicle Superf. Follicle & SCS

■

a^a

ns

■ ■

■ ■

ns

▲

Deep follicle

Superf. Follicle
& SCS

FIG. 21

U. S. Patent Jan. 10, 2017 Sheet 40 of 53                                    US 9, 539, 210 B2

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