dendritic cells & human therapy

[Guest guest]

The following three abstracts focus upon a new and very experimental way

to boost immunity in humans. Importantly, ex vivo dendritic cells can be

conditioned to be responsive to particular antigens.

My hunch is that the methods in these abstracts is boosting

immunological processes in ways akin to that utilized by HH Fudenberg,

M.D., in his classic autism-treatment study (4).

Kids for whom dendritic-cell therapy would be appropriate would probably

have to be very carefully chosen via medical history and extraordinarily

thorough medical-data matrices (immune panels, CBCs, and many etc).

ps: " Akin " in the above sentences means more " kinda sorta " and

definitely not " identical " or " nearly idendical " .

1: J Clin Immunol 2000 May;20(3):167-74

Active immunization of humans with dendritic cells.

Dhodapkar MV, Bhardwaj N

Laboratory of Cellular Physiology and Immunology, Rockefeller

University, New

York, New York 10021, USA.

Dendritic cells (DCs) are potent antigen-presenting cells specialized to

initiate T-cell immunity. The development of methods to generate large

numbers

of DCs has facilitated their application for immunotherapy. Recent

studies have

demonstrated the safety and immunogenicity of DCs in humans and have

begun to

outline the durability, kinetics, and nature of the elicited T-cell

responses.

However, DC-based immunotherapy remains a challenge and several

parameters need

to be examined to optimize immune responses, in order to maximize

clinical

efficacy against cancer and infectious diseases.

2: J Clin Invest 2000 Mar;105(6):R9-R14

Mature dendritic cells boost functionally superior CD8(+) T-cell in

humans

without foreign helper epitopes.

Dhodapkar MV, Krasovsky J, Steinman RM, Bhardwaj N

We have recently shown that a single injection of mature,

antigen-pulsed, human

dendritic cells (DCs) rapidly elicits CD4(+) and CD8(+) T-cell immunity

in vivo.

The DCs were pulsed with 2 foreign proteins, keyhole limpet hemocyanin

(KLH) and

tetanus toxoid (TT), as well as an HLA A2.1-restricted influenza matrix

peptide

(MP). Responses to all 3 antigens peaked at 30-90 days after

immunization and

declined thereafter. To determine if the foreign helper proteins (TT and

KLH)

were essential for CD8(+) T-cell responses to the viral peptide, we

reinjected 3

of the HLA-2.1 subjects with mature DCs pulsed with MP alone. All 3

volunteers

showed a rapid boost in MP-specific immunity, and freshly sampled blood

from 1

contained cytolytic T cells. In all 3 subjects, CD8(+) T-cell responses

to

booster DCs were faster and of greater magnitude than the responses to

the first

DC injection. Importantly, the T cells that proliferated after booster

DC

treatment secreted interferon-gamma upon challenge with much lower doses

of

viral peptide than those elicited after the first injection, indicating

a higher

functional avidity for the ligand. These data begin to outline the

kinetics of

T-cell immunity in response to DCs and demonstrate that booster

injections of

mature DCs enhance both qualitative and quantitative aspects of CD8(+)

T-cell

function in humans.

Comment in: J Clin Invest 2000 Mar;105(6):707-8

3: J Clin Invest 1999 Jul;104(2):173-80

Rapid generation of broad T-cell immunity in humans after a single

injection of

mature dendritic cells.

Dhodapkar MV, Steinman RM, Sapp M, Desai H, Fossella C, Krasovsky J,

Donahoe SM,

Dunbar PR, Cerundolo V, Nixon DF, Bhardwaj N

Dendritic cells (DCs) are potent antigen-presenting cells that initiate

protective T-cell immunity in mice. To study the immunogenicity of DCs

in

humans, we injected 9 healthy subjects subcutaneously with a control

injection

of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by

DCs

pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive

restricted

influenza matrix peptide (MP), and tetanus toxoid (TT). Four more

subjects

received these antigens without DCs. Injection of unpulsed DCs, or

antigens

alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed

in all

9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific

T-cell

immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs.

Injection of

antigen-pulsed DCs led to a severalfold increase in freshly isolated

MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6

HLA-A*0201-positive

subjects, as early as 7 days after injection. When T cells were boosted

in

culture, there was an increase in MHC tetramer-binding cells and

cytotoxic T

cells after DC vaccination. These data provide the first controlled

evidence of

the immunogenicity of DCs in humans, and demonstrate that a single

injection of

mature DCs rapidly expands T-cell immunity.

4.Biotherapy 1996;9(1-3):143-7

Dialysable lymphocyte extract (DLyE) in infantile onset autism: a pilot

study.

Fudenberg HH

40 infantile autistic patients were studied. They ranged from 6 years to

15

years of age at entry. 22 were cases of classical infantile autism;

whereas 18

lacked one or more clinical defects associated with infantile autism

( " pseudo-autism " ). Of the 22 with classic autism, 21 responded to

transfer

factor (TF) treatment by gaining at least 2 points in symptoms severity

score

average (SSSA); and 10 became normal in that they were main-streamed in

school

and clinical characteristics were fully normalized. Of the 18 remaining,

4

responded to TF, some to other therapies. After cessation of TF therapy,

5 in

the autistic group and 3 of the pseudo-autistic group regressed, but

they did

not drop as low as baseline levels.

Publication Types:

Clinical trial

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